Is CHRNE p.Ala362= (c.1086C>T) pathogenic?

CHRNE p.Ala362= (c.1086C>T) is classified Likely benign in CHRNE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). Very rare (popmax 0.00239%, eas); Associated with congenital myasthenic syndrome 4A.

What condition is associated with CHRNE p.Ala362= (c.1086C>T)?

CHRNE p.Ala362= (c.1086C>T) is associated with congenital myasthenic syndrome 4A (ClinVar).

How common is CHRNE p.Ala362= (c.1086C>T) in the general population?

CHRNE p.Ala362= (c.1086C>T) is very rare (popmax 0.00239%, eas) (gnomAD).

CHRNE p.Ala362=

c.1086C>T · rs1213521480 · VCV1642126

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00239%, eas)

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 -2.6	GERP -3.5
Overall
CADD	0.741	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00239% East Asian · 1/41,794 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000257% 4/1,553,862 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00239%	41,794
South Asian	0.00116%	86,134
European (non-Finnish)	0.000173%	578,305

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.Ala362=
Coding: c.1086C>T
MANE Select: NM_000080
dbSNP: rs1213521480
Type: single nucleotide variant
Location: chr17:4899331 (GRCh38)
Gene constraint: LOEUF 1.298 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 25 PDB

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.Ala362Asp Uncertain significance ★★ ⚠ same residue
CHRNE p.Ala362Gly Uncertain significance ★ ⚠ same residue
CHRNE p.Ala362Val Uncertain significance ★ ⚠ same residue
CHRNE p.Ala362fs Likely pathogenic ★ same residue
CHRNE p.Ala362Thr 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

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-ala362 (accessed [today's date]).

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