Is OCA2 p.Ala356Pro (c.1066G>C) pathogenic?

OCA2 p.Ala356Pro (c.1066G>C) is classified Uncertain significance in OCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-05). AlphaMissense: likely pathogenic (0.9607); Absent from gnomAD v4.1; Associated with oculocutaneous albinism type 2.

What condition is associated with OCA2 p.Ala356Pro (c.1066G>C)?

OCA2 p.Ala356Pro (c.1066G>C) is associated with oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Ala356Pro (c.1066G>C) in the general population?

OCA2 p.Ala356Pro (c.1066G>C) is absent from gnomAD v4.1 (gnomAD).

How is Oculocutaneous albinism type 2 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about OCA2 p.Ala356Pro (c.1066G>C)?

AlphaMissense predicts likely pathogenic (score 0.9607) — an in-silico prediction, not a clinical call.

OCA2 p.Ala356Pro

c.1066G>C · rs1246016828 · VCV3251960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9607 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocutaneous albinism type 2

Computational evidence

Protein change
AlphaMissense	0.9607	likely pathogenic · top 7% in OCA2
REVEL	0.859	moderately pathogenic-leaning
SaProt	LLR -14.24	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 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OCA2
Protein: p.Ala356Pro
Coding: c.1066G>C
MANE Select: NM_000275
dbSNP: rs1246016828
Type: single nucleotide variant
Location: chr15:27990626 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.79

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

Disease context

oculocutaneous albinism type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Oculocutaneous albinism type 2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 6-9 / 10 000 (Specific population)

Similar variants

OCA2 p.Ala356= Likely benign ★ same residue
OCA2 c.1044+1G>T Pathogenic ★★ same condition
OCA2 c.1045-15T>G Pathogenic/Likely pathogenic ★★ same condition
OCA2 c.1182+1G>A Pathogenic ★★ same condition
OCA2 c.1365-1G>A Pathogenic ★★ same condition
OCA2 c.1503+5G>A Pathogenic/Likely pathogenic ★★ same condition
OCA2 c.1504-2A>G Pathogenic/Likely pathogenic ★★ same condition
OCA2 c.1842+1G>T Pathogenic/Likely 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-ala356pro (accessed [today's date]).

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