CHRNA3 p.Phe324=
c.972C>T · rs200337870 · VCV2889697
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0319%, nfe)
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 -8.1 | GERP -5.7 |
| Overall | ||
| CADD | 1.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0319%
European (non-Finnish) · 377/1,180,034 alleles
Filtering AF
0.0293%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0282%
Overall
0.025%
404/1,614,036 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0319% | 3,130 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,249 |
| Admixed American | 0.01% | 9,999 |
| African / African-American | 0.00801% | 12,485 |
| South Asian | 0.00439% | 22,769 |
| Finnishnot grpmax-eligible | 0.00156% | 64,040 |
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.Phe324=
- Coding
- c.972C>T
- MANE Select
- NM_000743
- dbSNP
- rs200337870
- Type
- single nucleotide variant
- Location
- chr15:78601670 (GRCh38)
- Gene constraint
- LOEUF 1.065 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.97 · 5 PDB
- Residue 324
- an α-helix
Similar variants
- 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
- CHRNA3 p.Pro498Leu 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-phe324 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown