Is OCA2 p.Ser59fs (c.173_176dup) pathogenic?

OCA2 p.Ser59fs (c.173176dup) is classified Pathogenic/Likely pathogenic in OCA2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2024-03-29). Ultra-rare (popmax 0.0165%, mid); Associated with oculocutaneous albinism type 2.

What condition is associated with OCA2 p.Ser59fs (c.173_176dup)?

OCA2 p.Ser59fs (c.173_176dup) is associated with oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Ser59fs (c.173_176dup) in the general population?

OCA2 p.Ser59fs (c.173_176dup) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Oculocutaneous albinism type 2 inherited?

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

OCA2 p.Ser59fs

c.173_176dup · rs2548671260 · VCV2677407

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

oculocutaneous albinism type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.064

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.2e-05% 1/1,613,862 alleles · ultra-rare exomes 1/1,461,478 · genomes 0/152,384 · 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.Ser59fs
Coding: c.173_176dup
MANE Select: NM_000275
dbSNP: rs2548671260
Type: Microsatellite
Location: chr15:28081698 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.79
Residue 59: 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 p.363ALA[1] Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Glu125fs Pathogenic/Likely pathogenic ★★ same condition
OCA2 c.2245-3_2245-2del Likely pathogenic ★ same condition
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

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-ser59fs (accessed [today's date]).

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