Is OCA2 p.Pro211Ser (c.631C>T) pathogenic?

OCA2 p.Pro211Ser (c.631C>T) is classified Conflicting classifications of pathogenicity in OCA2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-06-10). AlphaMissense: likely benign (0.1084); Absent from gnomAD v4.1; Associated with SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES.

What condition is associated with OCA2 p.Pro211Ser (c.631C>T)?

OCA2 p.Pro211Ser (c.631C>T) is associated with SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES, oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Pro211Ser (c.631C>T) in the general population?

OCA2 p.Pro211Ser (c.631C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCA2 p.Pro211Ser (c.631C>T)?

AlphaMissense predicts likely benign (score 0.1084) — an in-silico prediction, not a clinical call.

OCA2 p.Pro211Ser

c.631C>T · VCV3339670

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1084 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES

Computational evidence

Protein change
AlphaMissense	0.1084	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -8.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	19.83	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.Pro211Ser
Coding: c.631C>T
MANE Select: NM_000275
Type: single nucleotide variant
Location: chr15:28022516 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.79
Residue 211: a UniProt-annotated variant site (in oca2; severe); a UniProt-annotated variant site (in oca2)

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

Disease context

SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oculocutaneous albinism type 2

Similar variants

OCA2 p.Pro211Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
OCA2 p.Pro211Ala Pathogenic/Likely pathogenic ★★ ⚠ same residue
OCA2 p.Pro211= Likely benign ★★ same residue
OCA2 c.1044+1G>T Pathogenic ★★ same condition
OCA2 c.1045-15T>G Pathogenic/Likely pathogenic ★★ same condition
OCA2 c.1116+2T>C Likely pathogenic ★★ same condition
OCA2 c.1182+1G>A 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-pro211ser (accessed [today's date]).

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