Is CLCN5 p.Phe459fs (c.1374del) pathogenic?

CLCN5 p.Phe459fs (c.1374del) is classified Pathogenic in CLCN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-24). No gnomAD frequency available for this variant; Associated with Inborn genetic diseases.

What condition is associated with CLCN5 p.Phe459fs (c.1374del)?

CLCN5 p.Phe459fs (c.1374del) is associated with Inborn genetic diseases (ClinVar).

How common is CLCN5 p.Phe459fs (c.1374del) in the general population?

CLCN5 p.Phe459fs (c.1374del) is no gnomAD frequency available for this variant (gnomAD).

CLCN5 p.Phe459fs

c.1374del · rs1557194018 · VCV521801

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLCN5
Protein: p.Phe459fs
Coding: c.1374del
MANE Select: NM_001127898
dbSNP: rs1557194018
Type: Deletion
Location: chrX:50086687 (GRCh38)
Structure: AlphaFold pLDDT 80.48 · 2 PDB

Full CLCN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLCN5 p.Ser110fs Pathogenic ★★ same condition
CLCN5 p.Phe459Leu Uncertain significance ★ ⚠ same residue
CLCN5 p.Ala319Val Uncertain significance ★★ ⚠ same condition
CLCN5 p.Ala806Val Uncertain significance ★★ ⚠ same condition
CLCN5 p.Arg372Cys Uncertain significance ★★ ⚠ same condition
CLCN5 p.Arg408Cys Uncertain significance ★★ ⚠ same condition
CLCN5 p.Arg696Trp Uncertain significance ★★ ⚠ same condition
CLCN5 p.Glu176Lys Uncertain significance ★★ ⚠ 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/clcn5-p-phe459fs (accessed [today's date]).

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