Is OCA2 p.Ser220Arg (c.660C>G) pathogenic?

OCA2 p.Ser220Arg (c.660C>G) is classified Uncertain significance in OCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-21). AlphaMissense: likely pathogenic (0.5701); Absent from gnomAD v4.1.

How common is OCA2 p.Ser220Arg (c.660C>G) in the general population?

OCA2 p.Ser220Arg (c.660C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCA2 p.Ser220Arg (c.660C>G)?

AlphaMissense predicts likely pathogenic (score 0.5701) — an in-silico prediction, not a clinical call.

OCA2 p.Ser220Arg

c.660C>G · rs2548453838 · VCV1717278

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5701 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5701	likely pathogenic
REVEL	0.216	benign-leaning
SaProt	LLR -8.22	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.27	GERP -2.4
Regional constraint	o/e 0.98	unconstrained · MANE · 326 kb · p 0.41 · regional, not allelic
Overall
CADD	6.344	PHRED · no single calibrated threshold — expert panels disagree

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.Ser220Arg
Coding: c.660C>G
MANE Select: NM_000275
dbSNP: rs2548453838
Type: single nucleotide variant
Location: chr15:28018544 (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.Ser220delinsThrTer Pathogenic ★ 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
OCA2 c.1365-1G>A 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-ser220arg (accessed [today's date]).

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