Is GABRB2 p.Arg293Gln (c.878G>A) pathogenic?

GABRB2 p.Arg293Gln (c.878G>A) is classified Likely pathogenic in GABRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). AlphaMissense: likely pathogenic (0.9744); Very rare (popmax 8.52e-05%, nfe); Associated with intellectual disability.

What condition is associated with GABRB2 p.Arg293Gln (c.878G>A)?

GABRB2 p.Arg293Gln (c.878G>A) is associated with intellectual disability (ClinVar).

How common is GABRB2 p.Arg293Gln (c.878G>A) in the general population?

GABRB2 p.Arg293Gln (c.878G>A) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

What do computational predictors say about GABRB2 p.Arg293Gln (c.878G>A)?

AlphaMissense predicts likely pathogenic (score 0.9744) — an in-silico prediction, not a clinical call.

GABRB2 p.Arg293Gln

c.878G>A · rs1210815997 · VCV2125918

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9744 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.9744	likely pathogenic ✓ concordant with ClinVar
REVEL	0.904	moderately pathogenic-leaning
SaProt	LLR -10.09	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 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 5,691 bp · p 8.7e-22 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,173,586 alleles

Overall 6.88e-05% 1/1,452,562 alleles · very rare

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: GABRB2
Protein: p.Arg293Gln
Coding: c.878G>A
MANE Select: NM_001371727
dbSNP: rs1210815997
Type: single nucleotide variant
Location: chr5:161331082 (GRCh38)
Gene constraint: LOEUF 0.426 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.65 · 31 PDB
Residue 293: a UniProt-annotated variant site (in iecee2; uncertain significance); an α-helix

Full GABRB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GABRB2 p.Arg293Trp Pathogenic/Likely pathogenic ★★ same residue
GABRB2 p.Arg293Pro Pathogenic ★ same residue
GABRB2 p.Ala304Val Pathogenic/Likely pathogenic ★★ same condition
GABRB2 p.Asp125Asn Pathogenic ★★ same condition
GABRB2 p.Ile288Thr Likely pathogenic ★★ same condition
GABRB2 p.Phe245Leu Pathogenic/Likely pathogenic ★★ same condition
GABRB2 p.Thr284Ile Pathogenic/Likely pathogenic ★★ same condition
GABRB2 p.Tyr301Cys 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/gabrb2-p-arg293gln (accessed [today's date]).

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