Is CHRNE p.Arg370= (c.1108A>C) pathogenic?

CHRNE p.Arg370= (c.1108A>C) is classified Likely benign in CHRNE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-20). Absent from gnomAD v4.1; Associated with congenital myasthenic syndrome 4A.

What condition is associated with CHRNE p.Arg370= (c.1108A>C)?

CHRNE p.Arg370= (c.1108A>C) is associated with congenital myasthenic syndrome 4A (ClinVar).

How common is CHRNE p.Arg370= (c.1108A>C) in the general population?

CHRNE p.Arg370= (c.1108A>C) is absent from gnomAD v4.1 (gnomAD).

CHRNE p.Arg370=

c.1108A>C · rs774315307 · VCV2713181

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,584,900)

Conditions

congenital myasthenic syndrome 4A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.23	GERP -3.1
Overall
CADD	7.887	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,584,900). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHRNE
Protein: p.Arg370=
Coding: c.1108A>C
MANE Select: NM_000080
dbSNP: rs774315307
Type: single nucleotide variant
Location: chr17:4899309 (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.Arg370fs Pathogenic/Likely pathogenic ★★ 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
CHRNE c.1220-2A>G Pathogenic/Likely pathogenic ★★ same condition
CHRNE c.1326+1G>A 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-arg370 (accessed [today's date]).

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