Is OCA2 p.Thr628fs (c.1880dup) pathogenic?

OCA2 p.Thr628fs (c.1880dup) is classified Likely pathogenic in OCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-31). Very rare (popmax 0.00133%, afr); Associated with OCA2-related disorder.

What condition is associated with OCA2 p.Thr628fs (c.1880dup)?

OCA2 p.Thr628fs (c.1880dup) is associated with OCA2-related disorder (ClinVar).

How common is OCA2 p.Thr628fs (c.1880dup) in the general population?

OCA2 p.Thr628fs (c.1880dup) is very rare (popmax 0.00133%, afr) (gnomAD).

OCA2 p.Thr628fs

c.1880dup · rs2140619003 · VCV4923607

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, 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 18 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.42	GERP 1.6, phastCons 0.031

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,058 alleles

Overall 0.000124% 2/1,614,060 alleles · very rare exomes 2/1,461,756 · genomes 0/152,304 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,504
African / African-Americangrpmax	0.00133%	75,058

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr628fs
Coding: c.1880dup
MANE Select: NM_000275
dbSNP: rs2140619003
Type: Duplication
Location: chr15:27951854 (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

Similar variants

OCA2 p.Ser148fs Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Ala424_Met425insAla Likely pathogenic ★ same condition
OCA2 p.Ala658fs Likely pathogenic ★ same condition
OCA2 p.Leu207fs Likely pathogenic ★ same condition
OCA2 p.Thr628Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-thr628fs (accessed [today's date]).

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