Is CLCN1 p.Pro698= (c.2094C>T) pathogenic?

CLCN1 p.Pro698= (c.2094C>T) is classified Likely benign in CLCN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-27). Very rare (popmax 0.00486%, nfe); Associated with myotonia congenita, autosomal dominant.

What condition is associated with CLCN1 p.Pro698= (c.2094C>T)?

CLCN1 p.Pro698= (c.2094C>T) is associated with myotonia congenita, autosomal dominant, myotonia congenita, autosomal recessive (ClinVar).

How common is CLCN1 p.Pro698= (c.2094C>T) in the general population?

CLCN1 p.Pro698= (c.2094C>T) is very rare (popmax 0.00486%, nfe) (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.Pro698=

c.2094C>T · rs758874120 · VCV697521

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00486%, nfe)

Conditions

myotonia congenita, autosomal dominant

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.1	GERP -5.5
Overall
CADD	1.787	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00486% European (non-Finnish) · 56/1,151,632 alleles

Filtering AF 0.00384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00379% 59/1,556,706 alleles · very rare exomes 59/1,404,492 · genomes 0/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00486%	20,565
South Asian	0.00237%	42,189
Remaining individualsnot grpmax-eligible	0.00166%	60,372

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.Pro698=
Coding: c.2094C>T
MANE Select: NM_000083
dbSNP: rs758874120
Type: single nucleotide variant
Location: chr7:143345684 (GRCh38)

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)

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-pro698 (accessed [today's date]).

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