Is CHRND p.Ser370fs (c.1107del) pathogenic?

CHRND p.Ser370fs (c.1107del) is classified Pathogenic/Likely pathogenic in CHRND (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-28). Very rare (popmax 0.0011%, sas); Associated with congenital myasthenic syndrome 3B.

What condition is associated with CHRND p.Ser370fs (c.1107del)?

CHRND p.Ser370fs (c.1107del) is associated with congenital myasthenic syndrome 3B, lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Ser370fs (c.1107del) in the general population?

CHRND p.Ser370fs (c.1107del) is very rare (popmax 0.0011%, sas) (gnomAD).

CHRND p.Ser370fs

c.1107del · rs1223709952 · VCV2162991

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

congenital myasthenic syndrome 3B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.4	GERP -3.7

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,066 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000411% 6/1,461,466 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,066
European (non-Finnish)	0.000424%	236,003

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.Ser370fs
Coding: c.1107del
MANE Select: NM_000751
dbSNP: rs1223709952
Type: Deletion
Location: chr2:232533988 (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 3B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lethal multiple pterygium syndrome

Similar variants

CHRND p.Ser370Thr Uncertain significance ★ ⚠ same residue
CHRND p.Asn456fs Uncertain significance ★★ same condition
CHRND c.820_820+1del Pathogenic ★ same condition
CHRND p.Ala13fs Pathogenic ★ same condition
CHRND p.Arg30fs Pathogenic ★ same condition
CHRND p.Asp186fs Likely pathogenic ★ same condition
CHRND p.Asp201fs Pathogenic ★ same condition
CHRND p.Glu71fs 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-ser370fs (accessed [today's date]).

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