Is CLCN1 p.Val605= (c.1815T>C) pathogenic?

CLCN1 p.Val605= (c.1815T>C) is classified Benign/Likely benign in CLCN1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-19). Rare (popmax 0.269%, afr); Associated with Batten-Turner congenital myopathy.

What condition is associated with CLCN1 p.Val605= (c.1815T>C)?

CLCN1 p.Val605= (c.1815T>C) is associated with Batten-Turner congenital myopathy, myotonia congenita, autosomal dominant, myotonia congenita, autosomal recessive (ClinVar).

How common is CLCN1 p.Val605= (c.1815T>C) in the general population?

CLCN1 p.Val605= (c.1815T>C) is rare (popmax 0.269%, afr) (gnomAD).

CLCN1 p.Val605=

c.1815T>C · rs141945240 · VCV392559

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.269%, afr)

Conditions

Batten-Turner congenital myopathy

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 -0.26	GERP 2.5, phastCons 0.48
Overall
CADD	5.627	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.269% African / African-American · 202/75,038 alleles

Filtering AF 0.239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.227%

Overall 0.0265% 428/1,614,166 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.269%	371
Middle Eastern	0.165%	606
Admixed American	0.065%	1,539
Remaining individualsnot grpmax-eligible	0.048%	2,084
European (non-Finnish)	0.0125%	8,027

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.Val605=
Coding: c.1815T>C
MANE Select: NM_000083
dbSNP: rs141945240
Type: single nucleotide variant
Location: chr7:143342390 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.34 · 9 PDB
Residue 605: an α-helix

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

Disease context

Batten-Turner congenital myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myotonia congenita, autosomal dominant myotonia congenita, autosomal recessive

Similar variants

CLCN1 p.Val605Ala 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
CLCN1 c.2172+1G>A 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-val605 (accessed [today's date]).

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