Is CHRNE p.Pro302Ser (c.904C>T) pathogenic?

CHRNE p.Pro302Ser (c.904C>T) is classified Uncertain significance in CHRNE (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-14). AlphaMissense: likely pathogenic (0.8011); Very rare (popmax 8.48e-05%, nfe).

How common is CHRNE p.Pro302Ser (c.904C>T) in the general population?

CHRNE p.Pro302Ser (c.904C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CHRNE p.Pro302Ser (c.904C>T)?

AlphaMissense predicts likely pathogenic (score 0.8011) — an in-silico prediction, not a clinical call.

CHRNE p.Pro302Ser

c.904C>T · rs979787967 · VCV2440054

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8011 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8011	likely pathogenic
REVEL	0.878	moderately pathogenic-leaning
SaProt	LLR -8.19	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 4,324 bp · p 7.4e-05 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,776 alleles

Overall 6.84e-05% 1/1,461,374 alleles · very rare

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: CHRNE
Protein: p.Pro302Ser
Coding: c.904C>T
MANE Select: NM_001145536 · reported on NM_000080
dbSNP: rs979787967
Type: single nucleotide variant
Location: chr17:4900806 (GRCh38)

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

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/chrne-p-pro302ser (accessed [today's date]).

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