Is OCA2 p.Phe385Ile (c.1153T>A) pathogenic?

OCA2 p.Phe385Ile (c.1153T>A) is classified Conflicting classifications of pathogenicity in OCA2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.2649); Rare (popmax 0.643%, afr); Associated with OCA2-related disorder.

What condition is associated with OCA2 p.Phe385Ile (c.1153T>A)?

OCA2 p.Phe385Ile (c.1153T>A) is associated with OCA2-related disorder, oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Phe385Ile (c.1153T>A) in the general population?

OCA2 p.Phe385Ile (c.1153T>A) is rare (popmax 0.643%, afr) (gnomAD).

What do computational predictors say about OCA2 p.Phe385Ile (c.1153T>A)?

AlphaMissense predicts likely benign (score 0.2649) — an in-silico prediction, not a clinical call.

OCA2 p.Phe385Ile

c.1153T>A · rs137956605 · VCV211765

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.2649 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.643%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

OCA2-related disorder

Computational evidence

Protein change
AlphaMissense	0.2649	likely benign
REVEL	0.634	indeterminate
SaProt	LLR -7.03	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	24.6	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 0.643% African / African-American · 483/75,060 alleles

Filtering AF 0.596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.577%

Overall 0.0325% 524/1,614,178 alleles · rare exomes 223/1,461,874 · genomes 301/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.643%	155
Admixed American	0.04%	2,501
Remaining individualsnot grpmax-eligible	0.024%	4,167
European (non-Finnish)	0.000169%	590,012

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.Phe385Ile
Coding: c.1153T>A
MANE Select: NM_000275
dbSNP: rs137956605
Type: single nucleotide variant
Location: chr15:27989630 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.79
Residue 385: a UniProt-annotated variant site (in oca2; severe)

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

Similar variants

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
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-phe385ile (accessed [today's date]).

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