Is GABRB2 p.Ser97Pro (c.289T>C) pathogenic?

GABRB2 p.Ser97Pro (c.289T>C) is classified Uncertain significance in GABRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: likely pathogenic (0.9922); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GABRB2 p.Ser97Pro (c.289T>C)?

GABRB2 p.Ser97Pro (c.289T>C) is associated with Inborn genetic diseases (ClinVar).

How common is GABRB2 p.Ser97Pro (c.289T>C) in the general population?

GABRB2 p.Ser97Pro (c.289T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GABRB2 p.Ser97Pro (c.289T>C)?

AlphaMissense predicts likely pathogenic (score 0.9922) — an in-silico prediction, not a clinical call.

GABRB2 p.Ser97Pro

c.289T>C · VCV4027723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9922 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9922	likely pathogenic
REVEL	0.687	pathogenic-leaning
SaProt	LLR -12.52	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 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 87 kb · p 7.5e-09 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Ser97Pro
Coding: c.289T>C
MANE Select: NM_001371727
Type: single nucleotide variant
Location: chr5:161459793 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GABRB2 p.Ala20Thr Uncertain significance ★★ ⚠ same condition
GABRB2 p.Arg141His Uncertain significance ★★ ⚠ same condition
GABRB2 p.Asp269His Uncertain significance ★★ ⚠ same condition
GABRB2 p.Val505Ile Uncertain significance ★★ ⚠ same condition
GABRB2 p.Asp80His Likely pathogenic ★ same condition
GABRB2 p.Gln209Pro Likely pathogenic ★ same condition
GABRB2 p.Thr280Ile Likely pathogenic ★ same condition
GABRB2 p.Arg470His Uncertain significance ★ ⚠ 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-ser97pro (accessed [today's date]).

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