Is CHRNE p.Phe155= (c.465C>T) pathogenic?

CHRNE p.Phe155= (c.465C>T) is classified Conflicting classifications of pathogenicity in CHRNE (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0758%, sas); Associated with congenital myasthenic syndrome.

What condition is associated with CHRNE p.Phe155= (c.465C>T)?

CHRNE p.Phe155= (c.465C>T) is associated with congenital myasthenic syndrome, congenital myasthenic syndrome 4A (ClinVar).

How common is CHRNE p.Phe155= (c.465C>T) in the general population?

CHRNE p.Phe155= (c.465C>T) is ultra-rare (popmax 0.0758%, sas) (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.Phe155=

c.465C>T · rs139625105 · VCV254898

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0758%, sas)

Conditions

congenital myasthenic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.6	GERP -1.1, phastCons 1
Overall
CADD	12.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0758% South Asian · 69/91,084 alleles

Filtering AF 0.0613% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0561%

Overall 0.0283% 456/1,614,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0758%	1,320
Middle Eastern	0.0329%	3,040
European (non-Finnish)	0.0311%	3,215
Remaining individualsnot grpmax-eligible	0.024%	4,166
African / African-American	0.00267%	37,465
Admixed American	0.00167%	60,004

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.Phe155=
Coding: c.465C>T
MANE Select: NM_001145536 · reported on NM_000080
dbSNP: rs139625105
Type: single nucleotide variant
Location: chr17:4901967 (GRCh38)

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)

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-phe155 (accessed [today's date]).

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