Is CLCN1 p.Phe314fs (c.942_960del) pathogenic?

CLCN1 p.Phe314fs (c.942960del) is classified Likely pathogenic in CLCN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). Associated with myotonia congenita, autosomal recessive.

What condition is associated with CLCN1 p.Phe314fs (c.942_960del)?

CLCN1 p.Phe314fs (c.942_960del) is associated with myotonia congenita, autosomal recessive, myotonia congenita, autosomal dominant (ClinVar).

How is Thomsen and Becker disease inherited?

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

CLCN1 p.Phe314fs

c.942_960del · VCV3594421

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

myotonia congenita, autosomal recessive

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 8 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 3.5, phastCons 1

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

Variant & gene context

Gene: CLCN1
Protein: p.Phe314fs
Coding: c.942_960del
MANE Select: NM_000083
Type: Deletion
Location: chr7:143330860 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.34 · 9 PDB
Residue 314: an α-helix

Full CLCN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

myotonia congenita, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myotonia congenita, autosomal dominant

For Thomsen and Becker disease (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

CLCN1 c.434-1_437del Pathogenic/Likely pathogenic ★★ same condition
CLCN1 p.Ala350fs Pathogenic/Likely pathogenic ★★ same condition
CLCN1 p.Gln675fs Pathogenic ★★ same condition
CLCN1 p.Glu624fs Pathogenic/Likely pathogenic ★★ same condition
CLCN1 p.Glu656fs Pathogenic/Likely pathogenic ★★ same condition
CLCN1 p.Gly11fs Pathogenic/Likely pathogenic ★★ same condition
CLCN1 p.Gly41fs Pathogenic/Likely pathogenic ★★ same condition
CLCN1 p.Leu121fs 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/clcn1-p-phe314fs (accessed [today's date]).

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