Is OCA2 p.Arg588Trp (c.1762C>T) pathogenic?

OCA2 p.Arg588Trp (c.1762C>T) is classified Conflicting classifications of pathogenicity in OCA2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1018); Rare (popmax 0.528%, sas); Associated with oculocutaneous albinism type 2.

What condition is associated with OCA2 p.Arg588Trp (c.1762C>T)?

OCA2 p.Arg588Trp (c.1762C>T) is associated with oculocutaneous albinism type 2, cone-rod dystrophy (ClinVar).

How common is OCA2 p.Arg588Trp (c.1762C>T) in the general population?

OCA2 p.Arg588Trp (c.1762C>T) is rare (popmax 0.528%, sas) (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.Arg588Trp (c.1762C>T)?

AlphaMissense predicts likely benign (score 0.1018) — an in-silico prediction, not a clinical call.

OCA2 p.Arg588Trp

c.1762C>T · rs150711896 · VCV885235

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1018 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.528%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocutaneous albinism type 2

Computational evidence

Protein change
AlphaMissense	0.1018	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -9.94	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 1.3	GERP -2.5, phastCons 0.14
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	23.3	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 0.528% South Asian · 481/91,064 alleles

Filtering AF 0.489% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.474%

Overall 0.0686% 1,106/1,612,730 alleles · rare exomes 1,010/1,460,424 · genomes 96/152,306 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.528%	189
Middle Eastern	0.502%	199
Remaining individualsnot grpmax-eligible	0.0944%	1,059
Admixed American	0.0566%	1,766
European (non-Finnish)	0.0409%	2,443
East Asian	0.0245%	4,079
African / African-American	0.0107%	9,380

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.Arg588Trp
Coding: c.1762C>T
MANE Select: NM_000275
dbSNP: rs150711896
Type: single nucleotide variant
Location: chr15:27957610 (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

Also linked: cone-rod dystrophy

For Oculocutaneous albinism type 2 (Orphanet):

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

Similar variants

OCA2 p.Arg588Gln Uncertain significance ★ ⚠ same residue
OCA2 p.Arg588= 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

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-arg588trp (accessed [today's date]).

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