Is GABRA2 p.Pro445Ser (c.1333C>T) pathogenic?

GABRA2 p.Pro445Ser (c.1333C>T) is classified Uncertain significance in GABRA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: likely benign (0.1744); Absent from gnomAD v4.1.

How common is GABRA2 p.Pro445Ser (c.1333C>T) in the general population?

GABRA2 p.Pro445Ser (c.1333C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GABRA2 p.Pro445Ser (c.1333C>T)?

AlphaMissense predicts likely benign (score 0.1744) — an in-silico prediction, not a clinical call.

GABRA2 p.Pro445Ser

c.1333C>T · rs2109372400 · VCV1699849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1744	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -5.70	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 7.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 12 kb · p 0.023 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: GABRA2
Protein: p.Pro445Ser
Coding: c.1333C>T
MANE Select: NM_000807
dbSNP: rs2109372400
Type: single nucleotide variant
Location: chr4:46250331 (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.Pro445His Uncertain significance ★ ⚠ same residue
GABRA2 p.Pro445Leu 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

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-pro445ser (accessed [today's date]).

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