Is OCA2 p.Arg136Ter (c.406C>T) pathogenic?

OCA2 p.Arg136Ter (c.406C>T) is classified Pathogenic in OCA2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-03-27). Ultra-rare (popmax 0.0134%, eas); Associated with oculocutaneous albinism.

What condition is associated with OCA2 p.Arg136Ter (c.406C>T)?

OCA2 p.Arg136Ter (c.406C>T) is associated with oculocutaneous albinism, oculocutaneous albinism type 2, hypophosphatasia (ClinVar).

How common is OCA2 p.Arg136Ter (c.406C>T) in the general population?

OCA2 p.Arg136Ter (c.406C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

OCA2 p.Arg136Ter

c.406C>T · rs201791790 · VCV2677399

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

oculocutaneous albinism

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 24
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.9	GERP -1.8, phastCons 0.18
Overall
CADD	34.0	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 0.0134% East Asian · 6/44,878 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00105% 17/1,614,210 alleles · ultra-rare exomes 15/1,461,878 · genomes 2/152,332 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.000763%	131,115

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.Arg136Ter
Coding: c.406C>T
MANE Select: NM_000275
dbSNP: rs201791790
Type: single nucleotide variant
Location: chr15:28027980 (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

oculocutaneous albinism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oculocutaneous albinism type 2 hypophosphatasia

Similar variants

OCA2 p.Arg136Gln Uncertain significance ★★ ⚠ same residue
OCA2 p.Arg136Pro Uncertain significance ★ ⚠ same residue
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

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-arg136ter (accessed [today's date]).

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