Is GABRB2 p.Ala112Val (c.335C>T) pathogenic?

GABRB2 p.Ala112Val (c.335C>T) is classified Uncertain significance in GABRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-20). AlphaMissense: likely pathogenic (0.9511); Absent from gnomAD v4.1; Associated with GABRB2-related neurodevelopmental disorders.

What condition is associated with GABRB2 p.Ala112Val (c.335C>T)?

GABRB2 p.Ala112Val (c.335C>T) is associated with GABRB2-related neurodevelopmental disorders (ClinVar).

How common is GABRB2 p.Ala112Val (c.335C>T) in the general population?

GABRB2 p.Ala112Val (c.335C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GABRB2 p.Ala112Val (c.335C>T)?

AlphaMissense predicts likely pathogenic (score 0.9511) — an in-silico prediction, not a clinical call.

GABRB2 p.Ala112Val

c.335C>T · rs2113263943 · VCV1328547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9511 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

GABRB2-related neurodevelopmental disorders

Computational evidence

Protein change
AlphaMissense	0.9511	likely pathogenic
REVEL	0.524	indeterminate
SaProt	LLR -8.87	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 87 kb · p 7.5e-09 · regional, not allelic
Overall
CADD	29.0	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: GABRB2
Protein: p.Ala112Val
Coding: c.335C>T
MANE Select: NM_001371727
dbSNP: rs2113263943
Type: single nucleotide variant
Location: chr5:161459747 (GRCh38)
Gene constraint: LOEUF 0.426 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.65 · 31 PDB
Residue 112: an α-helix

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

Disease context

GABRB2-related neurodevelopmental disorders

Similar variants

GABRB2 p.Phe224Cys Likely pathogenic ★ same condition
GABRB2 p.Pro252Ala Likely pathogenic ★ same condition
GABRB2 p.Ser437Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
GABRB2 p.Asn99Thr Uncertain significance ⚠ same condition
GABRB2 p.Ala304Val Pathogenic/Likely pathogenic ★★ same type
GABRB2 p.Arg293Trp Pathogenic/Likely pathogenic ★★ same type
GABRB2 p.Asp125Asn Pathogenic ★★ same type
GABRB2 p.Ile288Thr 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/gabrb2-p-ala112val (accessed [today's date]).

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