Is CHRNE p.Ser339= (c.1017C>G) pathogenic?

CHRNE p.Ser339= (c.1017C>G) is classified Benign in CHRNE (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.02%, afr); Associated with congenital myasthenic syndrome.

What condition is associated with CHRNE p.Ser339= (c.1017C>G)?

CHRNE p.Ser339= (c.1017C>G) is associated with congenital myasthenic syndrome, congenital myasthenic syndrome 4A (ClinVar).

How common is CHRNE p.Ser339= (c.1017C>G) in the general population?

CHRNE p.Ser339= (c.1017C>G) is low-frequency (popmax 3.02%, afr) (gnomAD).

How is Congenital myasthenic syndrome inherited?

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

CHRNE p.Ser339=

c.1017C>G · rs114454383 · VCV128760

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.02%, afr)

Conditions

congenital myasthenic syndrome

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 0.3	GERP -4.1, phastCons 0.95
Overall
CADD	3.804	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.02% African / African-American · 2,265/74,878 alleles

Filtering AF 2.92% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.88%

Overall 0.164% 2,621/1,598,656 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.02%	33
Admixed American	0.297%	337
Remaining individualsnot grpmax-eligible	0.233%	430
Middle Eastern	0.0866%	1,154
South Asian	0.0136%	7,342
European (non-Finnish)	0.00196%	51,053

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.Ser339=
Coding: c.1017C>G
MANE Select: NM_000080
dbSNP: rs114454383
Type: single nucleotide variant
Location: chr17:4899483 (GRCh38)
Gene constraint: LOEUF 1.298 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 25 PDB
Residue 339: 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

Also linked: congenital myasthenic syndrome 4A

For Congenital myasthenic syndrome (Orphanet):

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

Similar variants

CHRNE p.Ser339Phe 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
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-ser339 (accessed [today's date]).

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