Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Common
common (popmax 62.2%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
2
SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.40 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.7 | GERP 0.011, phastCons 1 |
| Overall | ||
| CADD | 8.204 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
62.2%
African / African-American · 46,659/74,962 alleles
Filtering AF
61.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 61.6%
Overall
43%
693,526/1,612,484 alleles · common
exomes 621,378/1,460,416 · genomes 72,148/152,068 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 62.2% | 2 |
| Middle Eastern | 53.2% | 2 |
| South Asian | 52.6% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 48.4% | 2 |
| Remaining individualsnot grpmax-eligible | 45.2% | 2 |
| East Asian | 42% | 2 |
| European (non-Finnish) | 41.5% | 2 |
| Admixed American | 38.6% | 3 |
| Finnishnot grpmax-eligible | 33.2% | 3 |
| Amishnot grpmax-eligible | 28.1% | 4 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- OCA2
- Protein
- p.Ala776=
- Coding
- c.2328T>C
- MANE Select
- NM_000275
- dbSNP
- rs1800419
- Type
- single nucleotide variant
- Location
- chr15:27851392 (GRCh38)
- Gene constraint
- LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.79
Similar variants
- OCA2 p.Ala776Asp Likely pathogenic ★ same residue
- OCA2 c.1044+1G>T Pathogenic ★★ same condition
- OCA2 c.1045-15T>G Pathogenic/Likely pathogenic ★★ same condition
- OCA2 c.1116+2T>C Likely pathogenic ★★ same condition
- OCA2 c.1182+1G>A Pathogenic ★★ same condition
- OCA2 c.1365-1G>A Pathogenic ★★ same condition
- OCA2 c.1503+5G>A Pathogenic/Likely pathogenic ★★ same condition
- OCA2 c.1504-2A>G Pathogenic/Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/oca2-p-ala776 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown