Is CHRNE p.Asp185= (c.555C>T) pathogenic?

CHRNE p.Asp185= (c.555C>T) is classified Benign/Likely benign in CHRNE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-06). Rare (popmax 0.266%, afr); Associated with congenital myasthenic syndrome 4A.

What condition is associated with CHRNE p.Asp185= (c.555C>T)?

CHRNE p.Asp185= (c.555C>T) is associated with congenital myasthenic syndrome 4A (ClinVar).

How common is CHRNE p.Asp185= (c.555C>T) in the general population?

CHRNE p.Asp185= (c.555C>T) is rare (popmax 0.266%, afr) (gnomAD).

CHRNE p.Asp185=

c.555C>T · rs137952354 · VCV516013

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.266%, 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 -8.5	GERP -3.5
Overall
CADD	0.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.266% African / African-American · 200/75,054 alleles

Filtering AF 0.236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.225%

Overall 0.0178% 288/1,614,188 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.266%	375
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Admixed American	0.0167%	6,002
European (non-Finnish)	0.00542%	18,438
South Asian	0.0011%	91,090

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.Asp185=
Coding: c.555C>T
MANE Select: NM_001145536 · reported on NM_000080
dbSNP: rs137952354
Type: single nucleotide variant
Location: chr17:4901571 (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-asp185 (accessed [today's date]).

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