Is OCA2 p.Ser494Phe (c.1481C>T) pathogenic?

OCA2 p.Ser494Phe (c.1481C>T) is classified Likely pathogenic in OCA2 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.8494); Very rare (popmax 0.00133%, afr); Associated with oculocutaneous albinism type 2.

What condition is associated with OCA2 p.Ser494Phe (c.1481C>T)?

OCA2 p.Ser494Phe (c.1481C>T) is associated with oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Ser494Phe (c.1481C>T) in the general population?

OCA2 p.Ser494Phe (c.1481C>T) is very rare (popmax 0.00133%, afr) (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.Ser494Phe (c.1481C>T)?

AlphaMissense predicts likely pathogenic (score 0.8494) — an in-silico prediction, not a clinical call.

OCA2 p.Ser494Phe

c.1481C>T · rs370239668 · VCV2430236

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8494 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocutaneous albinism type 2

Computational evidence

Protein change
AlphaMissense	0.8494	likely pathogenic ✓ concordant with ClinVar
REVEL	0.946	strongly pathogenic-leaning
SaProt	LLR -11.49	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 9.8	GERP 0.91, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	32.0	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 0.00133% African / African-American · 1/74,930 alleles

Overall 6.2e-05% 1/1,614,084 alleles · very rare exomes 0/1,461,892 · genomes 1/152,192 · joint denominator

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.Ser494Phe
Coding: c.1481C>T
MANE Select: NM_000275
dbSNP: rs370239668
Type: single nucleotide variant
Location: chr15:27983367 (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

For Oculocutaneous albinism type 2 (Orphanet):

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

Similar variants

OCA2 p.Ser494= 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
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-ser494phe (accessed [today's date]).

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