Is CLCN1 p.Val465Phe (c.1393G>T) pathogenic?

CLCN1 p.Val465Phe (c.1393G>T) is classified Likely pathogenic in CLCN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-15). AlphaMissense: likely benign (0.0818); Absent from gnomAD v4.1; Associated with Batten-Turner congenital myopathy.

What condition is associated with CLCN1 p.Val465Phe (c.1393G>T)?

CLCN1 p.Val465Phe (c.1393G>T) is associated with Batten-Turner congenital myopathy (ClinVar).

How common is CLCN1 p.Val465Phe (c.1393G>T) in the general population?

CLCN1 p.Val465Phe (c.1393G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLCN1 p.Val465Phe (c.1393G>T)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

CLCN1 p.Val465Phe

c.1393G>T · rs139158852 · VCV1202581

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Batten-Turner congenital myopathy

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign ⚠ discordant with ClinVar
REVEL	0.459	indeterminate
SaProt	LLR -7.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -7
Regional constraint	o/e 0.95	unconstrained · MANE · 36 kb · p 0.08 · regional, not allelic
Overall
CADD	0.266	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLCN1
Protein: p.Val465Phe
Coding: c.1393G>T
MANE Select: NM_000083
dbSNP: rs139158852
Type: single nucleotide variant
Location: chr7:143332865 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.34 · 9 PDB
Residue 465: 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

Similar variants

CLCN1 p.Val465Ile Uncertain significance ★★ ⚠ same residue
CLCN1 c.774+1G>A Pathogenic ★★ same condition
CLCN1 p.Ala531Val Pathogenic ★★ same condition
CLCN1 p.Arg317Gln Pathogenic/Likely pathogenic ★★ same condition
CLCN1 p.Arg894Ter Pathogenic/Likely pathogenic ★★ same condition
CLCN1 p.Cys254Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
CLCN1 p.Gln552Arg Pathogenic/Likely pathogenic ★★ same condition
CLCN1 p.Gly230Glu 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-val465phe (accessed [today's date]).

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