Is OCA2 p.Pro211Leu (c.632C>T) pathogenic?

OCA2 p.Pro211Leu (c.632C>T) is classified Conflicting classifications of pathogenicity in OCA2 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-05-30). AlphaMissense: likely benign (0.1822); Ultra-rare (popmax 0.0417%, amr); Associated with OCA2-related disorder.

What condition is associated with OCA2 p.Pro211Leu (c.632C>T)?

OCA2 p.Pro211Leu (c.632C>T) is associated with OCA2-related disorder, oculocutaneous albinism type 2, oculocutaneous albinism (ClinVar).

How common is OCA2 p.Pro211Leu (c.632C>T) in the general population?

OCA2 p.Pro211Leu (c.632C>T) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

What do computational predictors say about OCA2 p.Pro211Leu (c.632C>T)?

AlphaMissense predicts likely benign (score 0.1822) — an in-silico prediction, not a clinical call.

OCA2 p.Pro211Leu

c.632C>T · rs190612616 · VCV198064

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.1822 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

OCA2-related disorder

Computational evidence

Protein change
AlphaMissense	0.1822	likely benign
REVEL	0.705	pathogenic-leaning
SaProt	LLR -13.31	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.4	GERP 0.68, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	26.1	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 0.0417% Admixed American · 25/60,022 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00775% 125/1,613,010 alleles · ultra-rare exomes 116/1,460,750 · genomes 9/152,260 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,401
Remaining individualsnot grpmax-eligible	0.016%	6,246
East Asian	0.0134%	7,479
European (non-Finnish)	0.00662%	15,117
African / African-American	0.00401%	24,961
South Asian	0.0022%	45,533
Finnishnot grpmax-eligible	0.00156%	64,016

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.Pro211Leu
Coding: c.632C>T
MANE Select: NM_000275
dbSNP: rs190612616
Type: single nucleotide variant
Location: chr15:28022515 (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

OCA2-related disorder

Also linked: oculocutaneous albinism type 2 oculocutaneous albinism

Similar variants

OCA2 p.Pro211Ala Pathogenic/Likely pathogenic ★★ ⚠ same residue
OCA2 p.Pro211Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
OCA2 p.Pro211= 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

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-pro211leu (accessed [today's date]).

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