Is CHRNA3 p.Ala153= (c.459C>T) pathogenic?

CHRNA3 p.Ala153= (c.459C>T) is classified Likely benign in CHRNA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-07). Ultra-rare (popmax 0.0467%, amr); Associated with SMOKING AS A QUANTITATIVE TRAIT LOCUS 3.

What condition is associated with CHRNA3 p.Ala153= (c.459C>T)?

CHRNA3 p.Ala153= (c.459C>T) is associated with SMOKING AS A QUANTITATIVE TRAIT LOCUS 3, urinary bladder, atony of (ClinVar).

How common is CHRNA3 p.Ala153= (c.459C>T) in the general population?

CHRNA3 p.Ala153= (c.459C>T) is ultra-rare (popmax 0.0467%, amr) (gnomAD).

CHRNA3 p.Ala153=

c.459C>T · rs202207061 · VCV745151

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, amr)

Conditions

SMOKING AS A QUANTITATIVE TRAIT LOCUS 3

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 3	GERP 0.005, phastCons 1
Overall
CADD	12.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0467% Admixed American · 28/59,996 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0286%

Overall 0.00254% 41/1,613,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0467%	2,143
Remaining individualsnot grpmax-eligible	0.0064%	15,621
South Asian	0.0011%	91,084
European (non-Finnish)	0.000678%	147,502

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.Ala153=
Coding: c.459C>T
MANE Select: NM_000743
dbSNP: rs202207061
Type: single nucleotide variant
Location: chr15:78602183 (GRCh38)
Gene constraint: LOEUF 1.065 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.97 · 5 PDB
Residue 153: a β-strand

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

Disease context

SMOKING AS A QUANTITATIVE TRAIT LOCUS 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: urinary bladder, atony of

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-ala153 (accessed [today's date]).

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