Is CASK p.His358fs (c.1072del) pathogenic?

CASK p.His358fs (c.1072del) is classified Pathogenic in CASK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). Associated with Intellectual disability, CASK-related, X-linked.

What condition is associated with CASK p.His358fs (c.1072del)?

CASK p.His358fs (c.1072del) is associated with Intellectual disability, CASK-related, X-linked (ClinVar).

CASK p.His358fs

c.1072del · VCV3644942

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Intellectual disability, CASK-related, X-linked

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 12 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.2, phastCons 1

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

Variant & gene context

Gene: CASK
Protein: p.His358fs
Coding: c.1072del
MANE Select: NM_001367721
Type: Deletion
Location: chrX:41609987 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 358: the l27 1 domain; a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic)

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

Disease context

Intellectual disability, CASK-related, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASK p.His358Tyr Uncertain significance ★ ⚠ same residue
CASK c.1504-6del Benign/Likely benign ★★ same condition
CASK p.Arg526fs Pathogenic ★ same condition
CASK p.Glu153fs Pathogenic ★ same condition
CASK p.Met555fs Pathogenic ★ same condition
CASK c.2155+5_2155+6del Uncertain significance ★ same condition
CASK p.Asp10_Glu16del Uncertain significance ★ same condition
CASK c.1034-5del Benign ★ 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/cask-p-his358fs (accessed [today's date]).

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