Is CLCN4 p.Ser278fs (c.832del) pathogenic?

CLCN4 p.Ser278fs (c.832del) is classified Likely pathogenic in CLCN4 (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with intellectual disability, X-linked 49.

What condition is associated with CLCN4 p.Ser278fs (c.832del)?

CLCN4 p.Ser278fs (c.832del) is associated with intellectual disability, X-linked 49 (ClinVar).

How common is CLCN4 p.Ser278fs (c.832del) in the general population?

CLCN4 p.Ser278fs (c.832del) is absent from gnomAD (gnomAD).

CLCN4 p.Ser278fs

Q: How is CLCN4-related X-linked intellectual disability syndrome inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.832del · rs1924399093 · VCV983535

Likely pathogenic Single submitter

Classification

Likely 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

intellectual disability, X-linked 49

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 2.3, 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: CLCN4
Protein: p.Ser278fs
Coding: c.832del
MANE Select: NM_001830
dbSNP: rs1924399093
Type: Deletion
Location: chrX:10206765 (GRCh38)
Structure: AlphaFold pLDDT 84.66

Full CLCN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, X-linked 49 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLCN4-related X-linked intellectual disability syndrome (Orphanet):

Inheritance: X-linked dominant
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

CLCN4 p.Asn309fs Pathogenic ★ same condition
CLCN4 p.Asp125fs Likely pathogenic ★ same condition
CLCN4 p.Glu682fs Likely pathogenic ★ same condition
CLCN4 p.Phe123fs Pathogenic ★ same condition
CLCN4 p.Leu720fs Uncertain significance ★ same condition
CLCN4 p.Ser278Arg Uncertain significance ★ ⚠ same residue
CLCN4 p.Asp15fs Pathogenic same condition
CLCN4 p.Ala555Val 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/clcn4-p-ser278fs (accessed [today's date]).

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