Is GABRB2 p.Arg458= (c.1374A>G) pathogenic?

GABRB2 p.Arg458= (c.1374A>G) is classified Likely benign in GABRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-19). Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with GABRB2 p.Arg458= (c.1374A>G)?

GABRB2 p.Arg458= (c.1374A>G) is associated with intellectual disability (ClinVar).

How common is GABRB2 p.Arg458= (c.1374A>G) in the general population?

GABRB2 p.Arg458= (c.1374A>G) is absent from gnomAD v4.1 (gnomAD).

GABRB2 p.Arg458=

c.1374A>G · rs764850270 · VCV1586215

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual disability

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 1.5	GERP -1.2, phastCons 1
Overall
CADD	9.873	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: GABRB2
Protein: p.Arg458=
Coding: c.1374A>G
MANE Select: NM_001371727
dbSNP: rs764850270
Type: single nucleotide variant
Location: chr5:161294246 (GRCh38)
Gene constraint: LOEUF 0.426 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.65 · 31 PDB

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.Arg458Gln Likely benign ★★ same residue
GABRB2 p.Arg458Gly Uncertain significance ★ ⚠ same residue
GABRB2 p.Arg458Ter Uncertain significance ★ same residue
GABRB2 p.Ala304Val Pathogenic/Likely pathogenic ★★ same condition
GABRB2 p.Arg293Trp 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

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-arg458 (accessed [today's date]).

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