OCA2 p.Ser641=
c.1923G>A · rs534814000 · VCV1949518
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
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 -8.3 | GERP -3.2 |
| Overall | ||
| CADD | 0.123 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,870 alleles
Filtering AF
0.00435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.000496%
8/1,613,392 alleles · ultra-rare
exomes 7/1,461,192 · genomes 1/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,974 |
| European (non-Finnish) | 0.000254% | 393,130 |
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.Ser641=
- Coding
- c.1923G>A
- MANE Select
- NM_000275
- dbSNP
- rs534814000
- Type
- single nucleotide variant
- Location
- chr15:27951812 (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.Ser641Leu 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
- OCA2 c.1365-1G>A 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-ser641 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown