Is OCA2 p.Arg102Ser (c.306G>T) pathogenic?

OCA2 p.Arg102Ser (c.306G>T) is classified Uncertain significance in OCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-19). AlphaMissense: likely benign (0.2021); Very rare (popmax 0.0011%, sas).

How common is OCA2 p.Arg102Ser (c.306G>T) in the general population?

OCA2 p.Arg102Ser (c.306G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about OCA2 p.Arg102Ser (c.306G>T)?

AlphaMissense predicts likely benign (score 0.2021) — an in-silico prediction, not a clinical call.

OCA2 p.Arg102Ser

c.306G>T · rs2548508216 · VCV1716897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2021 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2021	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -5.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.36	donor loss, 20 bp away · masked 0 · deltas
Pangolin	Δ0.24	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.4	GERP -0.089, phastCons 0.82
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	17.82	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

Grpmax group 0.0011% South Asian · 1/91,062 alleles

Overall 6.2e-05% 1/1,613,678 alleles · very rare exomes 1/1,461,394 · genomes 0/152,284 · joint denominator

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.Arg102Ser
Coding: c.306G>T
MANE Select: NM_000275
dbSNP: rs2548508216
Type: single nucleotide variant
Location: chr15:28032085 (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 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
OCA2 c.1365-1G>A Pathogenic ★★ same type
OCA2 c.1503+5G>A Pathogenic/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-arg102ser (accessed [today's date]).

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