Is CHRNE p.Pro140= (c.420T>C) pathogenic?

CHRNE p.Pro140= (c.420T>C) is classified Likely benign in CHRNE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-16). Very rare (popmax 0.00667%, afr); Associated with congenital myasthenic syndrome 4A.

What condition is associated with CHRNE p.Pro140= (c.420T>C)?

CHRNE p.Pro140= (c.420T>C) is associated with congenital myasthenic syndrome 4A (ClinVar).

How common is CHRNE p.Pro140= (c.420T>C) in the general population?

CHRNE p.Pro140= (c.420T>C) is very rare (popmax 0.00667%, afr) (gnomAD).

CHRNE p.Pro140=

c.420T>C · rs886038226 · VCV254897

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

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 looked up on this page · why
Constraint at this position
Conservation	phyloP -0.23	GERP -4, phastCons 0.023
Overall
CADD	3.415	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,924 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000372% 6/1,613,930 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,985
European (non-Finnish)	8.47e-05%	1,180,034

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.Pro140=
Coding: c.420T>C
MANE Select: NM_001145536 · reported on NM_000080
dbSNP: rs886038226
Type: single nucleotide variant
Location: chr17:4902012 (GRCh38)

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

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-pro140 (accessed [today's date]).

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