GABRB2 p.Ile504=
c.1512C>T · rs761305470 · VCV2065888
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0121%, sas)
Conditions
1
intellectual disability
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 -0.1 | GERP -5.6, phastCons 0.049 |
| Overall | ||
| CADD | 8.056 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0121%
South Asian · 11/91,062 alleles
Filtering AF
0.00676%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00522%
Overall
0.00118%
19/1,613,192 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0121% | 8,278 |
| East Asian | 0.0111% | 8,974 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,462 |
| African / African-American | 0.00134% | 74,880 |
| European (non-Finnish) | 8.48e-05% | 1,179,350 |
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.Ile504=
- Coding
- c.1512C>T
- MANE Select
- NM_001371727
- dbSNP
- rs761305470
- Type
- single nucleotide variant
- Location
- chr5:161294108 (GRCh38)
- Gene constraint
- LOEUF 0.426 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.65 · 31 PDB
- Residue 504
- an α-helix
Similar variants
- GABRB2 p.Ile504Val Benign ★ 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
- GABRB2 p.Tyr301Cys 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-ile504 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown