Is CHRND p.Lys40= (c.120G>A) pathogenic?

CHRND p.Lys40= (c.120G>A) is classified Benign/Likely benign in CHRND (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.86%, nfe); Associated with congenital myasthenic syndrome.

What condition is associated with CHRND p.Lys40= (c.120G>A)?

CHRND p.Lys40= (c.120G>A) is associated with congenital myasthenic syndrome, lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Lys40= (c.120G>A) in the general population?

CHRND p.Lys40= (c.120G>A) is low-frequency (popmax 3.86%, nfe) (gnomAD).

How is Congenital myasthenic syndrome inherited?

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

CHRND p.Lys40=

c.120G>A · rs55921262 · VCV128756

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.86%, nfe)

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 3.8	GERP 0.72, phastCons 1
Overall
CADD	10.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.86% European (non-Finnish) · 45,602/1,180,014 alleles

Filtering AF 3.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.82%

Overall 3.46% 55,905/1,613,792 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	8.92%	11
Amishnot grpmax-eligible	4.61%	22
European (non-Finnish)grpmax	3.86%	26
Remaining individualsnot grpmax-eligible	2.88%	35
Admixed American	2.28%	44
Middle Eastern	1.73%	58
Ashkenazi Jewishnot grpmax-eligible	1.45%	69
African / African-American	0.584%	171
South Asian	0.486%	206
East Asian	0.00669%	14,956

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys40=
Coding: c.120G>A
MANE Select: NM_000751
dbSNP: rs55921262
Type: single nucleotide variant
Location: chr2:232526596 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB

Full CHRND 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: lethal multiple pterygium syndrome

For Congenital myasthenic syndrome (Orphanet):

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

Similar variants

CHRND p.Lys40Arg Uncertain significance ★ ⚠ same residue
CHRND p.Lys40Glu Uncertain significance ★ ⚠ 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

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-lys40 (accessed [today's date]).

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