Is CHRNE p.Ala337= (c.1011C>T) pathogenic?

CHRNE p.Ala337= (c.1011C>T) is classified Likely benign in CHRNE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). Very rare (popmax 8.51e-05%, nfe); Associated with congenital myasthenic syndrome 4A.

What condition is associated with CHRNE p.Ala337= (c.1011C>T)?

CHRNE p.Ala337= (c.1011C>T) is associated with congenital myasthenic syndrome 4A (ClinVar).

How common is CHRNE p.Ala337= (c.1011C>T) in the general population?

CHRNE p.Ala337= (c.1011C>T) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

CHRNE p.Ala337=

c.1011C>T · rs1555546423 · VCV465848

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Conditions

congenital myasthenic syndrome 4A

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 0.04	GERP 0.95
Overall
CADD	3.786	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,175,050 alleles

Overall 6.9e-05% 1/1,448,306 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.Ala337=
Coding: c.1011C>T
MANE Select: NM_000080
dbSNP: rs1555546423
Type: single nucleotide variant
Location: chr17:4899489 (GRCh38)
Gene constraint: LOEUF 1.298 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 25 PDB
Residue 337: an α-helix

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

Disease context

congenital myasthenic syndrome 4A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRNE p.Ala337Thr Uncertain significance ★ ⚠ same residue
CHRNE p.Ala337fs Pathogenic ★★ same residue
CHRNE p.Ala337Pro Uncertain significance ⚠ same residue
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

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-ala337 (accessed [today's date]).

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