CHRNA3 p.Ala461=
c.1383C>T · rs186011389 · VCV2724249
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.247%, eas)
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 2.9 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 7.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.247%
East Asian · 111/44,858 alleles
Filtering AF
0.21%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.196%
Overall
0.00955%
154/1,612,516 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.247% | 404 |
| Remaining individualsnot grpmax-eligible | 0.0417% | 2,401 |
| South Asian | 0.011% | 9,098 |
| African / African-American | 0.00401% | 24,963 |
| Admixed American | 0.00335% | 29,894 |
| European (non-Finnish) | 0.00017% | 589,518 |
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
- CHRNA3
- Protein
- p.Ala461=
- Coding
- c.1383C>T
- MANE Select
- NM_000743
- dbSNP
- rs186011389
- Type
- single nucleotide variant
- Location
- chr15:78601259 (GRCh38)
- Gene constraint
- LOEUF 1.065 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.97 · 5 PDB
- Residue 461
- a UniProt-annotated variant site (in baiprck; loss-of-function variant affecting ion transmembrane transport in response to acetylcholine; does not localize to plasma membrane); an α-helix
Similar variants
- CHRNA3 p.Ala461Thr Uncertain significance ★ ⚠ same residue
- CHRNA3 p.Trp180Ter Likely pathogenic ★★ same type
- CHRNA3 p.Arg477His Uncertain significance ★★ ⚠ same type
- CHRNA3 p.Asn92Ser Uncertain significance ★★ ⚠ same type
- CHRNA3 p.Asp230Asn Uncertain significance ★★ ⚠ same type
- CHRNA3 p.Gly390Ala Uncertain significance ★★ ⚠ same type
- CHRNA3 p.Gly493Ala Uncertain significance ★★ ⚠ same type
- CHRNA3 p.Leu380Val 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/chrna3-p-ala461 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown