Is OCA2 p.Arg136Pro (c.407G>C) pathogenic?

OCA2 p.Arg136Pro (c.407G>C) is classified Uncertain significance in OCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-13). AlphaMissense: likely benign (0.1041); Absent from gnomAD v4.1.

How common is OCA2 p.Arg136Pro (c.407G>C) in the general population?

OCA2 p.Arg136Pro (c.407G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCA2 p.Arg136Pro (c.407G>C)?

AlphaMissense predicts likely benign (score 0.1041) — an in-silico prediction, not a clinical call.

OCA2 p.Arg136Pro

c.407G>C · rs35764631 · VCV1716374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1041 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1041	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.6	GERP -2.4
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	0.137	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OCA2
Protein: p.Arg136Pro
Coding: c.407G>C
MANE Select: NM_000275
dbSNP: rs35764631
Type: single nucleotide variant
Location: chr15:28027979 (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

Similar variants

OCA2 p.Arg136Ter Pathogenic ★★ same residue
OCA2 p.Arg136Gln Uncertain significance ★★ ⚠ same residue
OCA2 c.1044+1G>T Pathogenic ★★ same type
OCA2 c.1044+2T>C Pathogenic/Likely pathogenic ★★ same type
OCA2 c.1045-15T>G Pathogenic/Likely pathogenic ★★ same type
OCA2 c.1116+2T>C Likely pathogenic ★★ same type
OCA2 c.1182+1G>A Pathogenic ★★ same type
OCA2 c.1239+2T>A Likely pathogenic ★★ same type

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-arg136pro (accessed [today's date]).

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