CHRNA3 p.Val66=
c.198G>A · rs878959316 · VCV2191403
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00878%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.75 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.61 | gain · loss 0.09 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 21.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00878%
South Asian · 8/91,094 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.000558%
9/1,614,026 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00878% | 11,387 |
| European (non-Finnish) | 8.47e-05% | 1,180,045 |
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.Val66=
- Coding
- c.198G>A
- MANE Select
- NM_000743
- dbSNP
- rs878959316
- Type
- single nucleotide variant
- Location
- chr15:78618800 (GRCh38)
- Gene constraint
- LOEUF 1.065 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.97 · 5 PDB
- Residue 66
- a β-strand
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-val66 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown