Is CLCN1 p.Asp712= (c.2136T>C) pathogenic?

CLCN1 p.Asp712= (c.2136T>C) is classified Benign/Likely benign in CLCN1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.85%, afr); Associated with myotonia congenita, autosomal recessive.

What condition is associated with CLCN1 p.Asp712= (c.2136T>C)?

CLCN1 p.Asp712= (c.2136T>C) is associated with myotonia congenita, autosomal recessive, myotonia congenita, autosomal dominant, Batten-Turner congenital myopathy (ClinVar).

How common is CLCN1 p.Asp712= (c.2136T>C) in the general population?

CLCN1 p.Asp712= (c.2136T>C) is low-frequency (popmax 2.85%, afr) (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.Asp712=

c.2136T>C · rs73726622 · VCV359117

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.85%, afr)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP 4.2, phastCons 1
Overall
CADD	9.924	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.85% African / African-American · 2,123/74,412 alleles

Filtering AF 2.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.71%

Overall 0.184% 2,914/1,587,048 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.85%	35
Admixed American	0.433%	231
Remaining individualsnot grpmax-eligible	0.302%	331
Middle Eastern	0.219%	456
European (non-Finnish)	0.0292%	3,424
South Asian	0.0104%	9,654
Finnishnot grpmax-eligible	0.00164%	61,162

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.Asp712=
Coding: c.2136T>C
MANE Select: NM_000083
dbSNP: rs73726622
Type: single nucleotide variant
Location: chr7:143345726 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.34 · 9 PDB

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 Batten-Turner congenital myopathy

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.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
CLCN1 c.2172+1G>A Pathogenic ★★ same condition
CLCN1 c.2172+1G>T 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-asp712 (accessed [today's date]).

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