Is OCA2 p.Ile349= (c.1047C>T) pathogenic?

OCA2 p.Ile349= (c.1047C>T) is classified Conflicting classifications of pathogenicity in OCA2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with OCA2 p.Ile349= (c.1047C>T)?

OCA2 p.Ile349= (c.1047C>T) is associated with Inborn genetic diseases, oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Ile349= (c.1047C>T) in the general population?

OCA2 p.Ile349= (c.1047C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

OCA2 p.Ile349=

c.1047C>T · rs767182132 · VCV255715

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

Inborn genetic diseases

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 -3.7	GERP -3.9
Overall
CADD	0.036	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00564% 91/1,613,608 alleles · ultra-rare exomes 77/1,461,442 · genomes 14/152,166 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.199%	502
Middle Easterngrpmax	0.0329%	3,041
Remaining individualsnot grpmax-eligible	0.0096%	10,413
East Asian	0.00668%	14,961
Finnishnot grpmax-eligible	0.00313%	31,916
South Asian	0.0022%	45,540
Admixed American	0.00167%	60,004
European (non-Finnish)	0.00136%	73,740

Ashkenazi Jewish 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.Ile349=
Coding: c.1047C>T
MANE Select: NM_000275
dbSNP: rs767182132
Type: single nucleotide variant
Location: chr15:27990645 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oculocutaneous albinism type 2

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-ile349 (accessed [today's date]).

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