OCA2 p.Pro750=
c.2250C>T · rs745593965 · VCV1642448
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -6.2 | GERP -3.6 |
| Overall | ||
| CADD | 0.354 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.00662%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00483%
Overall
0.00335%
54/1,612,640 alleles · ultra-rare
exomes 42/1,460,436 · genomes 12/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| Admixed American | 0.0134% | 7,486 |
| East Asian | 0.00892% | 11,210 |
| African / African-American | 0.00534% | 18,727 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,200 |
| Finnishnot grpmax-eligible | 0.00313% | 31,965 |
| European (non-Finnish) | 0.0028% | 35,741 |
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.Pro750=
- Coding
- c.2250C>T
- MANE Select
- NM_000275
- dbSNP
- rs745593965
- Type
- single nucleotide variant
- Location
- chr15:27851470 (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.Pro750fs Likely pathogenic ★ 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-pro750 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown