Is OCA2 p.Pro750fs (c.2247dup) pathogenic?

OCA2 p.Pro750fs (c.2247dup) is classified Likely pathogenic in OCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). No gnomAD frequency available for this variant; Associated with SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES.

What condition is associated with OCA2 p.Pro750fs (c.2247dup)?

OCA2 p.Pro750fs (c.2247dup) is associated with SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES (ClinVar).

How common is OCA2 p.Pro750fs (c.2247dup) in the general population?

OCA2 p.Pro750fs (c.2247dup) is no gnomAD frequency available for this variant (gnomAD).

OCA2 p.Pro750fs

c.2247dup · rs2505282185 · VCV3239996

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES

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 22 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: OCA2
Protein: p.Pro750fs
Coding: c.2247dup
MANE Select: NM_000275
dbSNP: rs2505282185
Type: Duplication
Location: chr15:27851472 (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

SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OCA2 p.Ala686fs Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Arg167fs Likely pathogenic ★ same condition
OCA2 p.Leu236fs Likely pathogenic ★ same condition
OCA2 p.Ser242fs Likely pathogenic ★ same condition
OCA2 p.Ser402fs Likely pathogenic ★ same condition
OCA2 p.Pro750= Likely benign ★ same residue
OCA2 c.1116+2T>C Likely pathogenic ★★ same condition
OCA2 c.1182+1G>A 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-pro750fs (accessed [today's date]).

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