Is OCA2 p.Ser148fs (c.440dup) pathogenic?

OCA2 p.Ser148fs (c.440dup) is classified Pathogenic/Likely pathogenic in OCA2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-08-08). Very rare (popmax 0.00534%, afr); Associated with OCA2-related disorder.

What condition is associated with OCA2 p.Ser148fs (c.440dup)?

OCA2 p.Ser148fs (c.440dup) is associated with OCA2-related disorder, oculocutaneous albinism (ClinVar).

How common is OCA2 p.Ser148fs (c.440dup) in the general population?

OCA2 p.Ser148fs (c.440dup) is very rare (popmax 0.00534%, afr) (gnomAD).

OCA2 p.Ser148fs

c.440dup · rs1057518192 · VCV373071

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

OCA2-related disorder

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 4 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.51	GERP -2.7, phastCons 0.002
Overall
CADD	19.64	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,940 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,082 alleles · very rare exomes 1/1,461,864 · genomes 3/152,218 · 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.Ser148fs
Coding: c.440dup
MANE Select: NM_000275
dbSNP: rs1057518192
Type: Duplication
Location: chr15:28027945 (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

OCA2-related disorder

Also linked: oculocutaneous albinism

Similar variants

OCA2 p.Ala424_Met425insAla Likely pathogenic ★ same condition
OCA2 p.Ala658fs Likely pathogenic ★ same condition
OCA2 p.Leu207fs Likely pathogenic ★ same condition
OCA2 p.Thr628fs Likely pathogenic ★ same condition
OCA2 c.1182+2dup Likely pathogenic same condition
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

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-ser148fs (accessed [today's date]).

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