Is GABRA2 p.Pro404Ala (c.1210C>G) pathogenic?

GABRA2 p.Pro404Ala (c.1210C>G) is classified Likely benign in GABRA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). AlphaMissense: likely benign (0.0576); Very rare (popmax 0.00134%, afr).

How common is GABRA2 p.Pro404Ala (c.1210C>G) in the general population?

GABRA2 p.Pro404Ala (c.1210C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about GABRA2 p.Pro404Ala (c.1210C>G)?

AlphaMissense predicts likely benign (score 0.0576) — an in-silico prediction, not a clinical call.

GABRA2 p.Pro404Ala

c.1210C>G · VCV3646960

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0576 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0576	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -7.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 7.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 12 kb · p 0.023 · regional, not allelic
Overall
CADD	22.3	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 0.00134% African / African-American · 1/74,834 alleles

Overall 6.85e-05% 1/1,460,372 alleles · very 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: GABRA2
Protein: p.Pro404Ala
Coding: c.1210C>G
MANE Select: NM_000807
Type: single nucleotide variant
Location: chr4:46250454 (GRCh38)
Gene constraint: LOEUF 0.49 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 83.71 · 15 PDB

Full GABRA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GABRA2 p.Pro404Thr Uncertain significance ★ ⚠ same residue
GABRA2 p.Ala332Val Pathogenic/Likely pathogenic ★★ same type
GABRA2 p.Pro280Leu Pathogenic/Likely pathogenic ★★ same type
GABRA2 p.Thr294Ile Pathogenic/Likely pathogenic ★★ same type
GABRA2 c.1059+1G>A Uncertain significance ★★ same type
GABRA2 c.1060-5643C>T Uncertain significance ★★ same type
GABRA2 c.1060-5644A>G Uncertain significance ★★ same type
GABRA2 p.Arg301Trp Uncertain significance ★★ ⚠ 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/gabra2-p-pro404ala (accessed [today's date]).

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