Is GABRB2 p.Ala436= (c.1308C>T) pathogenic?

GABRB2 p.Ala436= (c.1308C>T) is classified Benign in GABRB2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 26.4%, amr) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability.

What condition is associated with GABRB2 p.Ala436= (c.1308C>T)?

GABRB2 p.Ala436= (c.1308C>T) is associated with intellectual disability (ClinVar).

GABRB2 p.Ala436=

Q: How common is GABRB2 p.Ala436= (c.1308C>T) in the general population?

GABRB2 p.Ala436= (c.1308C>T) is common (popmax 26.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1308C>T · rs2229944 · VCV380805

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 26.4%, amr) — too common for a highly-penetrant pathogenic allele

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 -0.2	GERP -2.4, phastCons 0.045
Overall
CADD	6.676	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.4% Admixed American · 15,839/60,000 alleles

Filtering AF 26.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 25.9%

Overall 8.6% 138,818/1,614,038 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	26.4%	4
Middle Eastern	16.8%	6
African / African-American	15%	7
South Asian	11.1%	9
Remaining individualsnot grpmax-eligible	9.71%	10
Finnishnot grpmax-eligible	9.04%	11
Ashkenazi Jewishnot grpmax-eligible	8.76%	11
European (non-Finnish)	7.18%	14
Amishnot grpmax-eligible	6.25%	16
East Asian	3.08%	32

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.Ala436=
Coding: c.1308C>T
MANE Select: NM_001371727
dbSNP: rs2229944
Type: single nucleotide variant
Location: chr5:161294312 (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.Ala436Asp Uncertain significance ★ ⚠ same residue
GABRB2 p.Ala436Gly 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

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-ala436 (accessed [today's date]).

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