GABRA2 p.Pro59=
c.177A>C · VCV4797318
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.188 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 11.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,058 alleles
Filtering AF
8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000312%
5/1,604,646 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,058 |
| European (non-Finnish) | 0.000341% | 293,109 |
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.Pro59=
- Coding
- c.177A>C
- MANE Select
- NM_000807
- Type
- single nucleotide variant
- Location
- chr4:46386084 (GRCh38)
- Gene constraint
- LOEUF 0.49 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 83.71 · 15 PDB
- Residue 59
- a turn
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-pro59 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown