Is CLCN1 p.Ala331Leu (c.991_992delinsCT) pathogenic?

CLCN1 p.Ala331Leu (c.991992delinsCT) is classified Uncertain significance in CLCN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-12). Absent from gnomAD; Associated with myotonia congenita, autosomal recessive.

What condition is associated with CLCN1 p.Ala331Leu (c.991_992delinsCT)?

CLCN1 p.Ala331Leu (c.991_992delinsCT) is associated with myotonia congenita, autosomal recessive, myotonia congenita, autosomal dominant (ClinVar).

How common is CLCN1 p.Ala331Leu (c.991_992delinsCT) in the general population?

CLCN1 p.Ala331Leu (c.991_992delinsCT) is absent from gnomAD (gnomAD).

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.Ala331Leu

c.991_992delinsCT · rs2116852875 · VCV1498050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

myotonia congenita, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 3.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 36 kb · p 0.08 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLCN1
Protein: p.Ala331Leu
Coding: c.991_992delinsCT
MANE Select: NM_000083
dbSNP: rs2116852875
Type: Indel
Location: chr7:143331243 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.34 · 9 PDB
Residue 331: a β-strand

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 p.Ala331Ser Likely pathogenic ★★ ⚠ same residue
CLCN1 p.Ala331Gly Uncertain significance ★★ ⚠ same residue
CLCN1 p.Ala331fs Pathogenic ★ same residue
CLCN1 p.Ala331Thr Likely pathogenic ★ same residue
CLCN1 p.Ala331= Likely benign ★ same residue
CLCN1 p.Ala543Ile Uncertain significance ★★ same condition
CLCN1 p.Leu625_Leu628delinsVal Uncertain significance ★★ same condition
CLCN1 p.Leu684Gly Uncertain significance ★★ 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-ala331leu (accessed [today's date]).

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