Is GABRB2 p.Pro30Leu (c.89C>T) pathogenic?

GABRB2 p.Pro30Leu (c.89C>T) is classified Likely benign in GABRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-28). AlphaMissense: likely benign (0.187); Ultra-rare (popmax 0.0183%, amr); Associated with intellectual disability.

What condition is associated with GABRB2 p.Pro30Leu (c.89C>T)?

GABRB2 p.Pro30Leu (c.89C>T) is associated with intellectual disability (ClinVar).

How common is GABRB2 p.Pro30Leu (c.89C>T) in the general population?

GABRB2 p.Pro30Leu (c.89C>T) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about GABRB2 p.Pro30Leu (c.89C>T)?

AlphaMissense predicts likely benign (score 0.187) — an in-silico prediction, not a clinical call.

GABRB2 p.Pro30Leu

c.89C>T · rs749288718 · VCV863504

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.187 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.187	likely benign
REVEL	0.517	indeterminate
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 255 bp · p 0.88 · regional, not allelic
Overall
CADD	31.0	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 0.0183% Admixed American · 11/60,002 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.000682% 11/1,613,576 alleles · ultra-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.Pro30Leu
Coding: c.89C>T
MANE Select: NM_001371727
dbSNP: rs749288718
Type: single nucleotide variant
Location: chr5:161546402 (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.Pro30Ser 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
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-pro30leu (accessed [today's date]).

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