GABRB2 p.Pro400=
c.1200C>G · rs770453629 · VCV1582686
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
Conditions
1
intellectual disability
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.82 | GERP -4.2, phastCons 1 |
| Overall | ||
| CADD | 6.109 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,874 alleles
Filtering AF
0.000554%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000186%
3/1,610,932 alleles · very rare
exomes 3/1,458,732 · genomes 0/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,937 |
| South Asian | 0.0011% | 90,990 |
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.Pro400=
- Coding
- c.1200C>G
- MANE Select
- NM_001371727
- dbSNP
- rs770453629
- Type
- single nucleotide variant
- Location
- chr5:161294420 (GRCh38)
- Gene constraint
- LOEUF 0.426 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.65 · 31 PDB
Similar variants
- GABRB2 p.Pro400Thr Uncertain significance ★★ ⚠ same residue
- GABRB2 p.Pro400Leu 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-pro400 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown