Is GABRB3 p.Pro422= (c.1266G>T) pathogenic?

GABRB3 p.Pro422= (c.1266G>T) is classified Likely benign in GABRB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-15). Absent from gnomAD v4.1; Associated with epilepsy, childhood absence, susceptibility to, 1.

What condition is associated with GABRB3 p.Pro422= (c.1266G>T)?

GABRB3 p.Pro422= (c.1266G>T) is associated with epilepsy, childhood absence, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 5 (ClinVar).

How common is GABRB3 p.Pro422= (c.1266G>T) in the general population?

GABRB3 p.Pro422= (c.1266G>T) is absent from gnomAD v4.1 (gnomAD).

GABRB3 p.Pro422=

c.1266G>T · VCV3749251

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

epilepsy, childhood absence, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.96	GERP -5.1, phastCons 0.001
Overall
CADD	5.517	PHRED · no single calibrated threshold — expert panels disagree

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.Pro422=
Coding: c.1266G>T
MANE Select: NM_000814
Type: single nucleotide variant
Location: chr15:26547949 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.64 · 109 PDB

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

Disease context

epilepsy, childhood absence, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epilepsy, childhood absence, susceptibility to, 5

Similar variants

GABRB3 p.Pro422Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
GABRB3 p.Arg111Ter Pathogenic ★★ same condition
GABRB3 p.Arg194Ter Pathogenic ★★ same condition
GABRB3 p.Arg232Gln Pathogenic/Likely pathogenic ★★ same condition
GABRB3 p.Arg96Ser Pathogenic/Likely pathogenic ★★ same condition
GABRB3 p.Asp120Asn Pathogenic/Likely pathogenic ★★ same condition
GABRB3 p.Glu77Gln Likely pathogenic ★★ ⚠ same condition
GABRB3 p.Ile280Phe 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-pro422 (accessed [today's date]).

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