Is OCA2 p.Arg421fs (c.1262_1271del) pathogenic?

OCA2 p.Arg421fs (c.12621271del) is classified Pathogenic in OCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-13). No gnomAD frequency available for this variant.

How common is OCA2 p.Arg421fs (c.1262_1271del) in the general population?

OCA2 p.Arg421fs (c.1262_1271del) is no gnomAD frequency available for this variant (gnomAD).

OCA2 p.Arg421fs

c.1262_1271del · rs2548345604 · VCV2863854

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.5	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: OCA2
Protein: p.Arg421fs
Coding: c.1262_1271del
MANE Select: NM_000275
dbSNP: rs2548345604
Type: Deletion
Location: chr15:27985157 (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.Arg421Gln Uncertain significance ★★ ⚠ same residue
OCA2 p.Arg421Trp Uncertain significance ★★ ⚠ same residue
OCA2 p.Arg421= Likely benign ★ same residue
OCA2 c.647-12_647-1del Likely pathogenic ★★ same type
OCA2 p.Ala55fs Pathogenic/Likely pathogenic ★★ same type
OCA2 p.Ala696fs Pathogenic/Likely pathogenic ★★ same type
OCA2 p.Arg137fs Pathogenic ★★ same type
OCA2 p.Arg53fs 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-arg421fs (accessed [today's date]).

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