Is OCA2 p.Thr482Pro (c.1444A>C) pathogenic?

OCA2 p.Thr482Pro (c.1444A>C) is classified Conflicting classifications of pathogenicity in OCA2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-04-13). AlphaMissense: likely pathogenic (0.9329); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with OCA2 p.Thr482Pro (c.1444A>C)?

OCA2 p.Thr482Pro (c.1444A>C) is associated with Inborn genetic diseases, oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Thr482Pro (c.1444A>C) in the general population?

OCA2 p.Thr482Pro (c.1444A>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about OCA2 p.Thr482Pro (c.1444A>C)?

AlphaMissense predicts likely pathogenic (score 0.9329) — an in-silico prediction, not a clinical call.

OCA2 p.Thr482Pro

c.1444A>C · rs2041233832 · VCV1345031

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9329	likely pathogenic · top 10% in OCA2
REVEL	0.912	moderately pathogenic-leaning
SaProt	LLR -13.44	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 6.1	GERP 0.71, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	29.6	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 0.00267% African / African-American · 2/74,940 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,092 alleles · very rare exomes 1/1,461,882 · genomes 1/152,210 · 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.Thr482Pro
Coding: c.1444A>C
MANE Select: NM_000275
dbSNP: rs2041233832
Type: single nucleotide variant
Location: chr15:27983404 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oculocutaneous albinism type 2

Similar variants

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
OCA2 c.1842+2T>C 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-thr482pro (accessed [today's date]).

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