Is CHRNE p.Ser329Pro (c.985T>C) pathogenic?

CHRNE p.Ser329Pro (c.985T>C) is classified Uncertain significance in CHRNE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-19). AlphaMissense: likely pathogenic (0.8946); Absent from gnomAD v4.1; Associated with congenital myasthenic syndrome.

What condition is associated with CHRNE p.Ser329Pro (c.985T>C)?

CHRNE p.Ser329Pro (c.985T>C) is associated with congenital myasthenic syndrome (ClinVar).

How common is CHRNE p.Ser329Pro (c.985T>C) in the general population?

CHRNE p.Ser329Pro (c.985T>C) is absent from gnomAD v4.1 (gnomAD).

How is Congenital myasthenic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CHRNE p.Ser329Pro (c.985T>C)?

AlphaMissense predicts likely pathogenic (score 0.8946) — an in-silico prediction, not a clinical call.

CHRNE p.Ser329Pro

c.985T>C · rs2151095207 · VCV1328152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8946 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myasthenic syndrome

Computational evidence

Protein change
AlphaMissense	0.8946	likely pathogenic
REVEL	0.673	pathogenic-leaning
SaProt	LLR -14.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP -1, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 4,324 bp · p 7.4e-05 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHRNE
Protein: p.Ser329Pro
Coding: c.985T>C
MANE Select: NM_000080
dbSNP: rs2151095207
Type: single nucleotide variant
Location: chr17:4899515 (GRCh38)
Gene constraint: LOEUF 1.298 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 25 PDB
Residue 329: an α-helix

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

Disease context

congenital myasthenic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital myasthenic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

CHRNE c.1032+1G>A Likely pathogenic ★★ same condition
CHRNE c.1033-1G>C Pathogenic/Likely pathogenic ★★ same condition
CHRNE c.1033-2A>T Pathogenic/Likely pathogenic ★★ same condition
CHRNE c.1219+2T>G Pathogenic ★★ same condition
CHRNE c.1220-1G>C Pathogenic/Likely pathogenic ★★ same condition
CHRNE c.1220-2A>G Pathogenic/Likely pathogenic ★★ same condition
CHRNE c.1326+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHRNE p.Ala431Pro Pathogenic/Likely pathogenic ★★ 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/chrne-p-ser329pro (accessed [today's date]).

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