CHRNA6 p.Ser266=
c.798G>A · rs78464081 · VCV788868
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.81%, 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 |
|---|---|---|
| Pangolin | Δ0.26 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -6.9 | GERP -4.5 |
| Overall | ||
| CADD | 4.886 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.81%
African / African-American · 1,360/74,958 alleles
Filtering AF
1.73%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.7%
Overall
0.0955%
1,541/1,613,944 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.81% | 55 |
| Remaining individualsnot grpmax-eligible | 0.131% | 762 |
| Admixed American | 0.0867% | 1,154 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00659% | 15,178 |
| European (non-Finnish) | 0.00339% | 29,499 |
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
- CHRNA6
- Protein
- p.Ser266=
- Coding
- c.798G>A
- MANE Select
- NM_004198
- dbSNP
- rs78464081
- Type
- single nucleotide variant
- Location
- chr8:42756401 (GRCh38)
- Gene constraint
- LOEUF 1.053 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.06 · 2 PDB
- Residue 266
- a turn
Similar variants
- CHRNA6 p.Arg109His Uncertain significance ★ ⚠ same type
- CHRNA6 p.Arg330His Uncertain significance ★ ⚠ same type
- CHRNA6 p.Arg376Gly Uncertain significance ★ ⚠ same type
- CHRNA6 p.Arg96Cys Uncertain significance ★ ⚠ same type
- CHRNA6 p.Asn402His Uncertain significance ★ ⚠ same type
- CHRNA6 p.Asp119Asn Uncertain significance ★ ⚠ same type
- CHRNA6 p.Asp129Asn Uncertain significance ★ ⚠ same type
- CHRNA6 p.Asp187Ala 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/chrna6-p-ser266 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown