Is GABRB3 p.Arg232Pro (c.695G>C) pathogenic?

GABRB3 p.Arg232Pro (c.695G>C) is classified Likely pathogenic in GABRB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2014-04-14). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1; Associated with epilepsy, childhood absence, susceptibility to, 5.

What condition is associated with GABRB3 p.Arg232Pro (c.695G>C)?

GABRB3 p.Arg232Pro (c.695G>C) is associated with epilepsy, childhood absence, susceptibility to, 5 (ClinVar).

How common is GABRB3 p.Arg232Pro (c.695G>C) in the general population?

GABRB3 p.Arg232Pro (c.695G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GABRB3 p.Arg232Pro (c.695G>C)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

GABRB3 p.Arg232Pro

c.695G>C · rs797045045 · VCV209156

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

epilepsy, childhood absence, susceptibility to, 5

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 5% in GABRB3
REVEL	0.858	moderately pathogenic-leaning
SaProt	LLR -18.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.22	constrained · MANE · 19 kb · p 1.7e-21 · regional, not allelic
Overall
CADD	33.0	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: GABRB3
Protein: p.Arg232Pro
Coding: c.695G>C
MANE Select: NM_000814
dbSNP: rs797045045
Type: single nucleotide variant
Location: chr15:26567721 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.64 · 109 PDB
Residue 232: a UniProt-annotated variant site (found in patients with dravet syndrome; uncertain significance); a β-strand

Full GABRB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epilepsy, childhood absence, susceptibility to, 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GABRB3 p.Arg232Gln Pathogenic/Likely pathogenic ★★ same residue
GABRB3 p.Arg232Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
GABRB3 p.Arg232= Likely benign ★ same residue
GABRB3 p.Arg232Leu Uncertain significance ★ ⚠ same residue
GABRB3 p.Arg111Ter Pathogenic ★★ same condition
GABRB3 p.Arg194Ter Pathogenic ★★ same condition
GABRB3 p.Arg96Ser Pathogenic/Likely pathogenic ★★ same condition
GABRB3 p.Asp120Asn 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/gabrb3-p-arg232pro (accessed [today's date]).

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