CHRNA3 p.Pro333=
c.999G>A · rs138969500 · VCV2171051
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0947%, 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 -5.7 |
| Overall | ||
| CADD | 0.236 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0947%
African / African-American · 71/74,976 alleles
Filtering AF
0.077%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0705%
Overall
0.00558%
90/1,614,056 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0947% | 1,056 |
| South Asian | 0.00439% | 22,766 |
| Admixed American | 0.00333% | 30,005 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,252 |
| European (non-Finnish) | 0.000932% | 107,275 |
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.Pro333=
- Coding
- c.999G>A
- MANE Select
- NM_000743
- dbSNP
- rs138969500
- Type
- single nucleotide variant
- Location
- chr15:78601643 (GRCh38)
- Gene constraint
- LOEUF 1.065 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.97 · 5 PDB
- Residue 333
- a turn
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-pro333 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown