Is CHRNA3 p.Lys97= (c.291A>G) pathogenic?

CHRNA3 p.Lys97= (c.291A>G) is classified Benign in CHRNA3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Common (popmax 80.9%, amr) — too common for a highly-penetrant pathogenic allele; Associated with urinary bladder, atony of.

What condition is associated with CHRNA3 p.Lys97= (c.291A>G)?

CHRNA3 p.Lys97= (c.291A>G) is associated with urinary bladder, atony of (ClinVar).

CHRNA3 p.Lys97=

Q: How common is CHRNA3 p.Lys97= (c.291A>G) in the general population?

CHRNA3 p.Lys97= (c.291A>G) is common (popmax 80.9%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.291A>G · rs3743075 · VCV1209767

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 80.9%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

urinary bladder, atony of

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 -0.57	GERP -3.3, phastCons 0.022
Overall
CADD	8.318	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 80.9% Admixed American · 48,512/59,966 alleles

Filtering AF 80.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 80%

Overall 63.2% 1,016,988/1,610,160 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	80.9%	1
Middle Eastern	72.9%	1
South Asian	68.6%	1
Finnishnot grpmax-eligible	65.4%	2
Ashkenazi Jewishnot grpmax-eligible	64.2%	2
Remaining individualsnot grpmax-eligible	63.3%	2
European (non-Finnish)	62.3%	2
Amishnot grpmax-eligible	59.4%	2
East Asian	57.5%	2
African / African-American	56.5%	2

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.Lys97=
Coding: c.291A>G
MANE Select: NM_000743
dbSNP: rs3743075
Type: single nucleotide variant
Location: chr15:78617110 (GRCh38)
Gene constraint: LOEUF 1.065 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.97 · 5 PDB

Full CHRNA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

urinary bladder, atony of — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRNA3 p.Trp180Ter Likely pathogenic ★★ same condition
CHRNA3 p.Arg477His Uncertain significance ★★ ⚠ same condition
CHRNA3 p.Asn92Ser Uncertain significance ★★ ⚠ same condition
CHRNA3 p.Asp230Asn Uncertain significance ★★ ⚠ same condition
CHRNA3 p.Gly390Ala Uncertain significance ★★ ⚠ same condition
CHRNA3 p.Gly493Ala Uncertain significance ★★ ⚠ same condition
CHRNA3 p.Leu380Val Uncertain significance ★★ ⚠ same condition
CHRNA3 p.Pro498Leu Uncertain significance ★★ ⚠ same condition

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-lys97 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown