CHRNA5 p.Thr331=
c.993C>T · rs61740655 · VCV710275
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.86%, afr)
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 -20 | GERP -5.5 |
| Overall | ||
| CADD | 0.064 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.86%
African / African-American · 2,895/75,008 alleles
Filtering AF
3.74%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.69%
Overall
0.227%
3,667/1,614,090 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.86% | 26 |
| Amishnot grpmax-eligible | 0.987% | 101 |
| Middle Eastern | 0.61% | 164 |
| Admixed American | 0.415% | 241 |
| Remaining individualsnot grpmax-eligible | 0.366% | 273 |
| European (non-Finnish) | 0.0198% | 5,043 |
| South Asian | 0.0132% | 7,589 |
| East Asian | 0.00223% | 44,886 |
| Finnishnot grpmax-eligible | 0.00156% | 64,010 |
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
- CHRNA5
- Protein
- p.Thr331=
- Coding
- c.993C>T
- MANE Select
- NM_000745
- dbSNP
- rs61740655
- Type
- single nucleotide variant
- Location
- chr15:78590384 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.04
Similar variants
- CHRNA5 p.Thr331Ile Uncertain significance ★ ⚠ same residue
- CHRNA5 p.Gln18= Benign ★★ same type
- CHRNA5 p.Gly31= Benign ★★ same type
- CHRNA5 p.Leu363Gln Benign ★★ ⚠ same type
- CHRNA5 p.Lys167Arg Benign ★★ ⚠ same type
- CHRNA5 p.Thr359Met Likely benign ★★ same type
- CHRNA5 p.Tyr58= Benign ★★ same type
- CHRNA5 c.304-96C>A 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/chrna5-p-thr331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown