Is CLCN1 p.Ile329= (c.987C>T) pathogenic?

CLCN1 p.Ile329= (c.987C>T) is classified Likely benign in CLCN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). Rare (popmax 0.132%, mid); Associated with myotonia congenita, autosomal dominant.

What condition is associated with CLCN1 p.Ile329= (c.987C>T)?

CLCN1 p.Ile329= (c.987C>T) is associated with myotonia congenita, autosomal dominant, myotonia congenita, autosomal recessive (ClinVar).

How common is CLCN1 p.Ile329= (c.987C>T) in the general population?

CLCN1 p.Ile329= (c.987C>T) is rare (popmax 0.132%, mid) (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.Ile329=

c.987C>T · rs140664749 · VCV701892

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Conditions

myotonia congenita, autosomal dominant

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 1.1	GERP 2.7, phastCons 1
Overall
CADD	9.928	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Middle Eastern · 8/6,076 alleles

Filtering AF 0.0655% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.0101% 162/1,610,074 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	759
Ashkenazi Jewishnot grpmax-eligible	0.071%	1,409
South Asian	0.0253%	3,956
Admixed American	0.0167%	6,000
Remaining individualsnot grpmax-eligible	0.016%	6,237
European (non-Finnish)	0.00757%	13,218
East Asian	0.00223%	44,878

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: CLCN1
Protein: p.Ile329=
Coding: c.987C>T
MANE Select: NM_000083
dbSNP: rs140664749
Type: single nucleotide variant
Location: chr7:143331239 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.34 · 9 PDB
Residue 329: a β-strand; a UniProt-annotated variant site (in mcar)

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

Disease context

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

Also linked: myotonia congenita, autosomal recessive

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.Ile329_Thr330del Uncertain significance ★ same residue
CLCN1 p.Ile329Met Uncertain significance ★ ⚠ same residue
CLCN1 c.1167-10T>C Pathogenic/Likely pathogenic ★★ same condition
CLCN1 c.1401+1G>T Pathogenic/Likely pathogenic ★★ same condition
CLCN1 c.1471+1G>A Pathogenic/Likely pathogenic ★★ same condition
CLCN1 c.180+1G>A Likely pathogenic ★★ same condition
CLCN1 c.180+3A>T Pathogenic/Likely pathogenic ★★ same condition
CLCN1 c.1930+1G>A 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/clcn1-p-ile329 (accessed [today's date]).

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