README.md

metadata

license: mit

evoeval

A collection of genomic variant-effect evaluation datasets. Each dataset is a table of variants keyed on GRCh38 coordinates with a label and annotation columns, stored as Parquet. This repo holds the base (unscored) variant tables — model delta scores are computed downstream, not shipped here.

Standard column schema

Every parquet has these coordinate columns with standardized types:

Column	Type	Description
chrom	str	Chromosome, GRCh38, always chr-prefixed (e.g. chr1, chrX)
pos	int64	1-based VCF position
ref	str	Reference allele
alt	str	Alternate allele

Most datasets are also annotated with:

Column	Type	Description
genomic_element	str	Coarse location: CDS / splice_site / 5UTR / 3UTR / intron / ncRNA / intergenic
consequence	str	Most-severe SnpEff SO term from MANE Select transcripts (except where a dataset carries its own scheme — see per-dataset notes)
variant_type	str	SNV / insertion / deletion / MNV (derived from ref/alt lengths)

omim, gnomad_balanced, and the TraitGym sets carry their own pre-annotation scheme for consequence / genomic_element — see the individual sections.

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Dataset index

File	Task	n (total)	n pos	n neg
clinvar/clinvar.parquet	P/LP vs B/LB	200,036	66,987	133,049
splicevar/splicevar.parquet	Splice-altering vs Normal	11,978	7,147	4,831
gpn_star/cosmic.parquet	Somatic cancer mutations vs neutral	18,903	183	18,720
gpn_star/omim.parquet	Disease-associated vs common variants	2,640,672	406	2,640,266
gpn_star/gnomad_balanced.parquet	Balanced variant benchmark	11,992,284	5,996,146	5,996,138
traitgym/complex_traits.parquet	GWAS causal (non-coding) vs matched	11,400	1,140	10,260
traitgym/mendelian_traits.parquet	Mendelian disease causal vs matched	3,380	338	3,042

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ClinVar (clinvar/)

Source: ClinVar (GRCh38). Combined (un-split) variant table. Eval task: Distinguish Pathogenic/Likely Pathogenic from Benign/Likely Benign variants. Positive class: ClinSigSimple = 1 (P/LP) Negative class: ClinSigSimple = 0 (B/LB) Class balance: 66,987 positive : 133,049 negative

Columns

Column	Type	Notes
chrom	str	chr-prefixed
pos	int64
ref	str
alt	str
ClinSigSimple	int64	Label: 1 = P/LP, 0 = B/LB
ClinicalSignificance	str	Raw ClinVar significance text (5 distinct values)
ReviewStatus	str	ClinVar submission confidence tier (3 distinct values)
NumberSubmitters	int64	Number of submitting labs
GeneSymbol	str	Gene symbol
VariationID	int64	ClinVar variant identifier
feature_lvl2	str	Author-provided element annotation
genomic_element	str	SnpEff coarse element
consequence	str	SnpEff most-severe SO term (24 distinct values)
variant_type	str	SNV / insertion / deletion / MNV

Stratification

• genomic_element — CDS (124,449), intron (43,273), splice_site (16,910), 3UTR (7,488), intergenic (6,064), 5UTR (1,852)
• variant_type — SNV (173,657), deletion (16,975), insertion (9,114), MNV (290)
• consequence — 24 SnpEff SO strata

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SpliceVarDB (splicevar/)

Source: SpliceVarDB. Combined (un-split) variant table. Eval task: Distinguish experimentally confirmed splice-altering variants from normal (non-altering) variants. Positive class: classification = "Splice-altering" Negative class: classification = "Normal" Class balance: 7,147 positive : 4,831 negative. All variants are SNVs.

Columns

Column	Type	Notes
chrom	str	chr-prefixed
pos	int64	Genomic VCF position
ref	str
alt	str
classification	str	Label: "Splice-altering" or "Normal"
gene	str	Gene symbol
hgvs	str	HGVS notation
method	str	Experimental assay (RNA-Seq, MFASS, MaPSy, Minigene Assay, RT-PCR, …)
location	str	"Intronic", "Exonic", or "Exonic,Intronic"
is_coding	bool	Whether the variant falls in coding sequence
genomic_element	str	SnpEff coarse element
consequence	str	SnpEff most-severe SO term
variant_type	str	All SNV

Stratification

• method — RNA-Seq (6,117), MFASS (5,022), MaPSy (326), Minigene Assay (296), RT-PCR (119), Unspecified (45), plus a few combined-assay values
• location — Intronic (7,407), Exonic (4,338), Exonic,Intronic (233)
• is_coding — True (8,201) / False (3,777)

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GPN-star benchmarks (gpn_star/)

Source: songlab/gpn-star on HuggingFace. Pre-computed model scores (GPN-MSA, CADD, phyloP, phastCons, ESM-1b, NT) have been stripped; these are the base variant tables.

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cosmic.parquet — COSMIC somatic mutations vs neutral variants

Eval task: Distinguish COSMIC-catalogued somatic cancer mutations from common neutral variants. Positive class: label = True — COSMIC-catalogued somatic cancer mutation Negative class: label = False — common benign missense variant (gnomAD, AF > 5%) Class balance: 183 positive : 18,720 negative (102:1)

Column	Type	Notes
chrom	str	chr-prefixed
pos	int64
ref	str
alt	str
label	bool	Label: True = COSMIC cancer mutation
consequence	str	SnpEff most-severe SO term
genomic_element	str	SnpEff coarse element
variant_type	str	All SNV

Important caveat: 180 of 183 positives (98%) are missense_variant in CDS. All other genomic_element/consequence strata have 0 or 3 positives. Stratified AUCs will mostly return None; the overall AUC is the meaningful metric here.

Stratification

• genomic_element — only CDS (180 pos) and intergenic (3 pos) have any positives.
• consequence — only missense_variant (180 pos) and intergenic_region (3 pos) have positives.

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omim.parquet — OMIM disease-associated variants vs common variants

Eval task: Distinguish OMIM-listed regulatory disease variants from common population variants. Positive class: label = True — OMIM-curated pathogenic regulatory variant Negative class: label = False — common variant (gnomAD, AF > 5%) Class balance: 406 positive : 2,640,266 negative (6,500:1)

Column	Type	Notes
chrom	str	chr-prefixed
pos	int64
ref	str
alt	str
label	bool	Label: True = OMIM disease-associated
consequence	str	Custom OMIM categories (not SnpEff SO terms)
variant_type	str	All SNV
genomic_element	str	Mapped from custom consequence (see below)

Custom consequence values and their genomic_element mapping:

consequence	genomic_element	n total	n pos
Enhancer	intergenic	2,357,316	37
ncRNA	ncRNA	137,330	60
3' UTR	3UTR	68,413	38
Promoter	intergenic	62,575	130
5' UTR	5UTR	15,030	133
MicroRNA Gene	ncRNA	5	5
Imprinting Control Region	intergenic	3	3

All variants are non-coding regulatory elements. The Enhancer category dominates (89% of rows) with very sparse positives (37 of 2.36M).

Stratification

• genomic_element — 4 strata, all ≥20 rows with both classes: intergenic (170 pos), ncRNA (65), 3UTR (38), 5UTR (133).
• consequence — 5 valid strata: Enhancer (37), ncRNA (60), 3' UTR (38), Promoter (130), 5' UTR (133).

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gnomad_balanced.parquet — gnomAD balanced benchmark

Eval task: General variant-effect prediction benchmark using gnomAD population variants. Positive class: label = True — rare variant (singleton in gnomAD, under purifying selection) Negative class: label = False — common variant (AF > 5% in gnomAD, likely neutral) Class balance: 5,996,146 : 5,996,138 (perfectly balanced, 50:50)

Label semantics (GPN-star paper, Benegas et al. 2024): True = gnomAD singleton; False = common variant (AF > 5%). Purifying selection keeps deleterious variants rare, so rare variants are enriched for functional/deleterious effect. A model with signal assigns more negative delta scores to singletons than to common variants.

Column	Type	Notes
chrom	str	chr-prefixed
pos	int64
ref	str
alt	str
label	bool	Label: True/False (see note above)
consequence	str	Simplified consequence terms (see below)
variant_type	str	All SNV
genomic_element	str	Mapped from simplified consequence

Simplified consequence values and their genomic_element mapping (top strata):

consequence	genomic_element	n total	n pos	n neg
intron	intron	6,481,608	3,240,804	3,240,804
intergenic	intergenic	4,714,558	2,357,279	2,357,279
non_coding_transcript_exon	ncRNA	274,540	137,270	137,270
3_prime_UTR	3UTR	136,750	68,375	68,375
downstream_gene	intergenic	129,544	64,772	64,772
upstream_gene	intergenic	124,890	62,445	62,445
synonymous	CDS	37,948	18,974	18,974
missense	CDS	37,452	18,726	18,726
5_prime_UTR	5UTR	29,794	14,897	14,897
splice_region	splice_site	24,170	12,085	12,085

Consequence terms are simplified (not standard SO format): intron not intron_variant, missense not missense_variant. Perfectly balanced within every stratum (pos/neg equal or off by 1).

Stratification

• genomic_element — 7 strata, all perfectly balanced and ≥20 rows.
• consequence — 13 valid strata, all perfectly balanced.

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TraitGym (traitgym/)

Source: songlab/TraitGym on HuggingFace. Eval task: Distinguish causal variants from matched controls selected within the same functional category with similar MAF and LD score — the model cannot win on consequence or frequency bias alone. Positive class: label = True (causal variant) Negative class: label = False (matched control)

Annotation: Pre-annotated by the TraitGym authors using ENCODE regulatory-element categories (dELS, pELS, PLS, …) combined with SO terms — these are kept as-is (SnpEff annotation is deliberately not applied, as it would overwrite the informative ENCODE categories).

Consequence categories used:

Term	Meaning
PLS	Promoter-like signature (ENCODE cRE)
pELS	Proximal enhancer-like signature
dELS	Distal enhancer-like signature
pELS_flank, dELS_flank	Flanking regions of ELS elements
intron_variant, intergenic_variant, non_coding_transcript_exon_variant, 3_prime_UTR_variant, 5_prime_UTR_variant, upstream_gene_variant	SO terms

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complex_traits.parquet — GWAS fine-mapped non-coding variants

Eval task: GWAS fine-mapped causal non-coding variants vs matched controls. Class balance: 1,140 causal : 10,260 controls (1:9)

Column	Type	Notes
chrom	str	chr-prefixed
pos	int64
ref	str
alt	str
pip	float64	Posterior inclusion probability (causal prior)
trait	str	GWAS trait name (empty string "" for controls)
label	bool	Label: True = causal
maf	float64	Minor allele frequency
ld_score	float64	LD score
consequence	str	ENCODE/SO category (see above)
tss_dist	int64	Distance to nearest transcription start site
match_group	str	Matching group ID (each causal paired with controls)

trait is empty string for all controls — per-trait stratification would create causal-only strata, so it is excluded from stratification.

Stratification

• consequence — 15 valid strata: dELS (314 pos), intron_variant (190), dELS_flank (167), intergenic_variant (103), pELS (101), … Each stratum keeps the 1:9 pos:neg ratio by design.

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mendelian_traits.parquet — Mendelian disease regulatory variants

Eval task: Mendelian disease regulatory causal variants vs matched controls (promoters, UTRs, ncRNA from OMIM). Class balance: 338 causal : 3,042 controls (1:9)

Column	Type	Notes
chrom	str	chr-prefixed
pos	int64
ref	str
alt	str
OMIM	str	OMIM gene/disease ID (NaN for controls)
consequence	str	ENCODE/SO category (see above)
label	bool	Label: True = disease-causing
tss_dist	int64	Distance to nearest TSS
match_group	str	Matching group ID

Stratification

• consequence — 11 valid strata: 5_prime_UTR_variant (114 pos), non_coding_transcript_exon_variant (71), PLS (63), 3_prime_UTR_variant (29), upstream_gene_variant (21), … Smaller counts — some strata will have low power.