OCA2 p.Ala14=
c.42G>A · rs762670171 · VCV2421559
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0317%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.2 | |
| Overall | ||
| CADD | 1.402 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0317%
Admixed American · 19/59,962 alleles
Filtering AF
0.0207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0172%
Overall
0.00515%
83/1,611,536 alleles · ultra-rare
exomes 78/1,459,316 · genomes 5/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0317% | 3,156 |
| Middle Eastern | 0.0165% | 6,068 |
| Remaining individualsnot grpmax-eligible | 0.00802% | 12,472 |
| South Asian | 0.00659% | 15,172 |
| African / African-American | 0.00534% | 18,734 |
| European (non-Finnish) | 0.00398% | 25,101 |
| East Asian | 0.00223% | 44,874 |
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.Ala14=
- Coding
- c.42G>A
- MANE Select
- NM_000275
- dbSNP
- rs762670171
- Type
- single nucleotide variant
- Location
- chr15:28081833 (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.Ala14Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
- OCA2 p.Ala14Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- OCA2 c.1044+1G>T Pathogenic ★★ same type
- OCA2 c.1044+2T>C Pathogenic/Likely pathogenic ★★ same type
- OCA2 c.1045-15T>G Pathogenic/Likely pathogenic ★★ same type
- OCA2 c.1116+2T>C Likely pathogenic ★★ same type
- OCA2 c.1182+1G>A Pathogenic ★★ same type
- OCA2 c.1239+2T>A Likely pathogenic ★★ same type
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-ala14 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown