Is OCA2 p.Ala334Val (c.1001C>T) pathogenic?

OCA2 p.Ala334Val (c.1001C>T) is classified Pathogenic/Likely pathogenic in OCA2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-18). AlphaMissense: likely pathogenic (0.8227); Very rare (popmax 0.0022%, sas); Associated with OCA2-related disorder.

What condition is associated with OCA2 p.Ala334Val (c.1001C>T)?

OCA2 p.Ala334Val (c.1001C>T) is associated with OCA2-related disorder, oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Ala334Val (c.1001C>T) in the general population?

OCA2 p.Ala334Val (c.1001C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about OCA2 p.Ala334Val (c.1001C>T)?

AlphaMissense predicts likely pathogenic (score 0.8227) — an in-silico prediction, not a clinical call.

OCA2 p.Ala334Val

c.1001C>T · rs121918168 · VCV958

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely pathogenic

0.8227 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

OCA2-related disorder

Computational evidence

Protein change
AlphaMissense	0.8227	likely pathogenic ✓ concordant with ClinVar
REVEL	0.742	pathogenic-leaning
SaProt	LLR -12.44	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,076 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000991% 16/1,613,900 alleles · very rare exomes 15/1,461,812 · genomes 1/152,088 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,538
European (non-Finnish)	0.00119%	84,288

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.Ala334Val
Coding: c.1001C>T
MANE Select: NM_000275
dbSNP: rs121918168
Type: single nucleotide variant
Location: chr15:28014819 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.79
Residue 334: a UniProt-annotated variant site (in oca2)

Full OCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

OCA2-related disorder

Also linked: oculocutaneous albinism type 2

Similar variants

OCA2 p.Ala334Thr Pathogenic/Likely pathogenic ★★ same residue
OCA2 p.Ala334= Likely benign ★ same residue
OCA2 c.1044+1G>T Pathogenic ★★ same condition
OCA2 c.1044+2T>C Pathogenic/Likely pathogenic ★★ same condition
OCA2 c.1045-15T>G Pathogenic/Likely pathogenic ★★ same condition
OCA2 c.1182+1G>A Pathogenic ★★ same condition
OCA2 c.1239+2T>A Likely pathogenic ★★ same condition
OCA2 c.1365-1G>A 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-ala334val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown