Is OCA2 p.Ala42= (c.126C>T) pathogenic?

OCA2 p.Ala42= (c.126C>T) is classified Benign/Likely benign in OCA2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.15%, afr); Associated with oculocutaneous albinism type 2.

What condition is associated with OCA2 p.Ala42= (c.126C>T)?

OCA2 p.Ala42= (c.126C>T) is associated with oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Ala42= (c.126C>T) in the general population?

OCA2 p.Ala42= (c.126C>T) is low-frequency (popmax 1.15%, afr) (gnomAD).

How is Oculocutaneous albinism type 2 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

OCA2 p.Ala42=

c.126C>T · rs141135991 · VCV887202

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, afr)

Conditions

oculocutaneous albinism type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.42
Overall
CADD	2.439	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.15% African / African-American · 862/75,060 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.06%

Overall 0.0597% 963/1,613,396 alleles · low-frequency exomes 466/1,461,042 · genomes 497/152,354 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.15%	87
Remaining individualsnot grpmax-eligible	0.0769%	1,300
Admixed American	0.0583%	1,714
South Asian	0.00988%	10,118
East Asian	0.00223%	44,868
European (non-Finnish)	0.000678%	147,486

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.Ala42=
Coding: c.126C>T
MANE Select: NM_000275
dbSNP: rs141135991
Type: single nucleotide variant
Location: chr15:28081749 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.79
Residue 42: the 'disordered' region

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-ala42 (accessed [today's date]).

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