| --- |
| license: cc-by-4.0 |
| task_categories: |
| - tabular-classification |
| language: |
| - en |
| tags: |
| - biology |
| - genomics |
| - clinical-genetics |
| - missense-variants |
| - loss-of-function |
| - gain-of-function |
| - variant-effect-prediction |
| - benchmark |
| - precision-medicine |
| size_categories: |
| - 100K<n<1M |
| --- |
| |
| # GLOF: A large-scale expert-curated benchmark of missense variant functional effects |
|
|
| GLOF (Gain and Loss Of Function) is a benchmark dataset of **112,399 missense variants** across **2,809 human genes**, each classified as **LOF** (loss-of-function), **GOF** (gain-of-function), or **Neutral** by board-certified clinical geneticists. |
|
|
| ## Dataset Description |
|
|
| The dataset was curated at [Mendelics Analise Genomica](https://www.mendelics.com/), one of Latin America's largest clinical genomics laboratories. The annotation process integrated ClinVar pathogenicity classifications, published functional studies, established gene-disease relationships, and expert clinical judgment following ACMG/AMP guidelines. |
|
|
| - **Pathogenic variants** were sourced from ClinVar (July 2023 release) and cross-referenced against the March 2026 release; variants with reclassified or conflicting evidence were excluded. |
| - **Neutral variants** were drawn from gnomAD v3.1 and validated against v4.1 allele frequencies, selecting missense variants with AF > 1%. |
|
|
| ## Dataset Schema |
|
|
| | Field | Type | Description | |
| |-------|------|-------------| |
| | VARIANTKEY | String | Unique variant identifier: `chr-position-ref-alt` (GRCh38) | |
| | LABEL | String | Functional classification: `Neutral`, `LOF`, or `GOF` | |
| | ENSG | String | Ensembl gene identifier | |
| | GENE_SYMBOL | String | HGNC gene symbol | |
| | AA_POSITION | Integer | Amino acid substitution position in the canonical protein | |
| | PROTEIN_REF | Character | Reference (wild-type) amino acid | |
| | PROTEIN_ALT | Character | Alternate (mutant) amino acid | |
|
|
| ## Class Distribution |
|
|
| | Class | Variants | Percentage | Genes | |
| |-------|----------|------------|-------| |
| | Neutral | 83,902 | 74.6% | 2,749 | |
| | LOF | 25,368 | 22.6% | 2,020 | |
| | GOF | 3,129 | 2.8% | 260 | |
|
|
| ## Usage |
|
|
| ```python |
| from datasets import load_dataset |
| |
| dataset = load_dataset("victormaricato/glof") |
| ``` |
|
|
| ## License |
|
|
| This dataset is released under the [CC BY 4.0](https://creativecommons.org/licenses/by/4.0/) license. |
|
|
