Is OCA2 p.Arg352Ser (c.1056A>C) pathogenic?

OCA2 p.Arg352Ser (c.1056A>C) is classified Likely pathogenic in OCA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-03-07). AlphaMissense: likely pathogenic (0.9805); Absent from gnomAD v4.1; Associated with Nonsyndromic Oculocutaneous Albinism.

What condition is associated with OCA2 p.Arg352Ser (c.1056A>C)?

OCA2 p.Arg352Ser (c.1056A>C) is associated with Nonsyndromic Oculocutaneous Albinism (ClinVar).

How common is OCA2 p.Arg352Ser (c.1056A>C) in the general population?

OCA2 p.Arg352Ser (c.1056A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCA2 p.Arg352Ser (c.1056A>C)?

AlphaMissense predicts likely pathogenic (score 0.9805) — an in-silico prediction, not a clinical call.

OCA2 p.Arg352Ser

c.1056A>C · rs1566767423 · VCV617803

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9805 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Nonsyndromic Oculocutaneous Albinism

Computational evidence

Protein change
AlphaMissense	0.9805	likely pathogenic ✓ concordant with ClinVar · top 4% in OCA2
REVEL	0.784	moderately pathogenic-leaning
SaProt	LLR -14.61	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 -0.085	GERP -3.9, phastCons 0.83
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	21.7	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

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.Arg352Ser
Coding: c.1056A>C
MANE Select: NM_000275
dbSNP: rs1566767423
Type: single nucleotide variant
Location: chr15:27990636 (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

Nonsyndromic Oculocutaneous Albinism

Similar variants

OCA2 p.Arg352Gly Uncertain significance ★ ⚠ same residue
OCA2 p.Arg352= 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.1239+2T>A Likely pathogenic ★★ same condition
OCA2 c.1503+5G>A Pathogenic/Likely pathogenic ★★ same condition
OCA2 c.1504-2A>G 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-arg352ser (accessed [today's date]).

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