Is OCA2 p.Arg243Cys (c.727C>T) pathogenic?

OCA2 p.Arg243Cys (c.727C>T) is classified Conflicting classifications of pathogenicity in OCA2 (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.1045); Rare (popmax 0.125%, eas); Associated with oculocutaneous albinism.

What condition is associated with OCA2 p.Arg243Cys (c.727C>T)?

OCA2 p.Arg243Cys (c.727C>T) is associated with oculocutaneous albinism, oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Arg243Cys (c.727C>T) in the general population?

OCA2 p.Arg243Cys (c.727C>T) is rare (popmax 0.125%, eas) (gnomAD).

What do computational predictors say about OCA2 p.Arg243Cys (c.727C>T)?

AlphaMissense predicts likely benign (score 0.1045) — an in-silico prediction, not a clinical call.

OCA2 p.Arg243Cys

c.727C>T · rs138065338 · VCV198411

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.1045 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.125%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

oculocutaneous albinism

Computational evidence

Protein change
AlphaMissense	0.1045	likely benign
REVEL	0.34	indeterminate
SaProt	LLR -9.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.58	GERP -0.48
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	11.37	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 0.125% East Asian · 56/44,884 alleles

Filtering AF 0.0986% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0892%

Overall 0.0167% 270/1,613,786 alleles · rare exomes 234/1,461,472 · genomes 36/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.125%	802
Ashkenazi Jewishnot grpmax-eligible	0.0676%	1,480
South Asian	0.0483%	2,069
Middle Eastern	0.033%	3,028
Remaining individualsnot grpmax-eligible	0.0256%	3,905
European (non-Finnish)	0.0105%	9,515
African / African-American	0.00933%	10,720
Admixed American	0.00167%	60,016

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.Arg243Cys
Coding: c.727C>T
MANE Select: NM_000275
dbSNP: rs138065338
Type: single nucleotide variant
Location: chr15:28018477 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oculocutaneous albinism type 2

Similar variants

OCA2 p.Arg243His Uncertain significance ★ ⚠ 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-arg243cys (accessed [today's date]).

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