Is OCA2 p.Ala336Val (c.1007C>T) pathogenic?

OCA2 p.Ala336Val (c.1007C>T) is classified Benign/Likely benign in OCA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0609); Low-frequency (popmax 2.42%, afr); Associated with oculocutaneous albinism type 2.

What condition is associated with OCA2 p.Ala336Val (c.1007C>T)?

OCA2 p.Ala336Val (c.1007C>T) is associated with oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Ala336Val (c.1007C>T) in the general population?

OCA2 p.Ala336Val (c.1007C>T) is low-frequency (popmax 2.42%, 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.Ala336Val (c.1007C>T)?

AlphaMissense predicts likely benign (score 0.0609) — an in-silico prediction, not a clinical call.

OCA2 p.Ala336Val

c.1007C>T · rs34010619 · VCV255713

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0609 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.42%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocutaneous albinism type 2

Computational evidence

Protein change
AlphaMissense	0.0609	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -4.62	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 0.85	GERP -3.5, phastCons 0.096
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	5.436	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 2.42% African / African-American · 1,812/75,012 alleles

Filtering AF 2.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.29%

Overall 0.126% 2,032/1,613,984 alleles · low-frequency exomes 978/1,461,744 · genomes 1,054/152,240 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.42%	41
Admixed American	0.165%	606
Remaining individualsnot grpmax-eligible	0.162%	619
Middle Eastern	0.0165%	6,062
South Asian	0.0022%	45,529
European (non-Finnish)	0.00144%	69,413

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.Ala336Val
Coding: c.1007C>T
MANE Select: NM_000275
dbSNP: rs34010619
Type: single nucleotide variant
Location: chr15:28014813 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.79
Residue 336: a UniProt-annotated variant site (in)

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 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-ala336val (accessed [today's date]).

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