OCA2 p.Phe407=
c.1221C>T · rs370349105 · VCV1618232
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0353%, sas)
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 0.029 | GERP -3.5, phastCons 0.1 |
| Overall | ||
| CADD | 11.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0353%
South Asian · 32/90,696 alleles
Filtering AF
0.0257%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0223%
Overall
0.00616%
98/1,590,670 alleles · ultra-rare
exomes 88/1,438,468 · genomes 10/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0353% | 2,834 |
| Admixed American | 0.02% | 4,999 |
| Remaining individualsnot grpmax-eligible | 0.00648% | 15,430 |
| European (non-Finnish) | 0.00414% | 24,133 |
| African / African-American | 0.00268% | 37,349 |
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.Phe407=
- Coding
- c.1221C>T
- MANE Select
- NM_000275
- dbSNP
- rs370349105
- Type
- single nucleotide variant
- Location
- chr15:27986605 (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 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
- OCA2 c.1503+5G>A Pathogenic/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-phe407 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown