GABRA2 p.Pro376=
c.1128G>A · rs201736133 · VCV1919218
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0017%, nfe)
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 -5.3 | GERP -5.4 |
| Overall | ||
| CADD | 7.231 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0017%
European (non-Finnish) · 20/1,178,466 alleles
Filtering AF
0.00111%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000901%
Overall
0.00137%
22/1,611,466 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0017% | 58,923 |
| Admixed American | 0.00167% | 59,704 |
| South Asian | 0.0011% | 91,028 |
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.Pro376=
- Coding
- c.1128G>A
- MANE Select
- NM_000807
- dbSNP
- rs201736133
- Type
- single nucleotide variant
- Location
- chr4:46250536 (GRCh38)
- Gene constraint
- LOEUF 0.49 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 83.71 · 15 PDB
Similar variants
- 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
- GABRA2 p.Arg56Trp 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-pro376 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown