Is CHRND p.Arg243Cys (c.727C>T) pathogenic?

CHRND p.Arg243Cys (c.727C>T) is classified Conflicting classifications of pathogenicity in CHRND (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.2804); Low-frequency (popmax 1.47%, mid); Associated with congenital myasthenic syndrome 3A.

What condition is associated with CHRND p.Arg243Cys (c.727C>T)?

CHRND p.Arg243Cys (c.727C>T) is associated with congenital myasthenic syndrome 3A, lethal multiple pterygium syndrome, congenital myasthenic syndrome 3B (ClinVar).

How common is CHRND p.Arg243Cys (c.727C>T) in the general population?

CHRND p.Arg243Cys (c.727C>T) is low-frequency (popmax 1.47%, mid) (gnomAD).

What do computational predictors say about CHRND p.Arg243Cys (c.727C>T)?

AlphaMissense predicts likely benign (score 0.2804) — an in-silico prediction, not a clinical call.

CHRND p.Arg243Cys

c.727C>T · rs201733876 · VCV283138

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.2804 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.47%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myasthenic syndrome 3A

Computational evidence

Protein change
AlphaMissense	0.2804	likely benign
REVEL	0.662	pathogenic-leaning
SaProt	LLR -12.79	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,093 bp · p 0.12 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.47% Middle Eastern · 89/6,062 alleles

Filtering AF 1.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.13%

Overall 0.0292% 472/1,614,166 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.47%	68
African / African-American	0.0786%	1,272
Admixed American	0.0766%	1,305
Remaining individualsnot grpmax-eligible	0.056%	1,786
European (non-Finnish)	0.0197%	5,086
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
South Asian	0.00549%	18,215
East Asian	0.00446%	22,439

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: CHRND
Protein: p.Arg243Cys
Coding: c.727C>T
MANE Select: NM_000751
dbSNP: rs201733876
Type: single nucleotide variant
Location: chr2:232530046 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 243: a β-strand

Full CHRND gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 3A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lethal multiple pterygium syndrome congenital myasthenic syndrome 3B congenital myasthenic syndrome 3C congenital myasthenic syndrome

Similar variants

CHRND p.Arg243His Conflicting classifications of pathogenicity ★ ⚠ same residue
CHRND c.1252+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHRND c.821-2A>C Pathogenic/Likely pathogenic ★★ same condition
CHRND c.933-2A>G Likely pathogenic ★★ same condition
CHRND p.Arg336Gln Likely pathogenic ★★ same condition
CHRND p.Arg43Trp Pathogenic/Likely pathogenic ★★ same condition
CHRND p.Cys257Arg Pathogenic/Likely pathogenic ★★ same condition
CHRND p.Trp78Ter 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/chrnd-p-arg243cys (accessed [today's date]).

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