Is CASK p.Val292del (c.875_877del) pathogenic?

CASK p.Val292del (c.875877del) is classified Likely pathogenic in CASK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-09-10). Absent from gnomAD; Associated with syndromic X-linked intellectual disability Najm type.

What condition is associated with CASK p.Val292del (c.875_877del)?

CASK p.Val292del (c.875_877del) is associated with syndromic X-linked intellectual disability Najm type, intellectual disability (ClinVar).

How common is CASK p.Val292del (c.875_877del) in the general population?

CASK p.Val292del (c.875_877del) is absent from gnomAD (gnomAD).

How is X-linked intellectual disability, Najm type inherited?

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

CASK p.Val292del

c.875_877del · rs2066559023 · VCV981293

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

syndromic X-linked intellectual disability Najm type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1

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: CASK
Protein: p.Val292del
Coding: c.875_877del
MANE Select: NM_001367721
dbSNP: rs2066559023
Type: Deletion
Location: chrX:41636616 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 292: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); an α-helix

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

Disease context

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

Also linked: intellectual disability

For X-linked intellectual disability, Najm type (Orphanet):

Inheritance: X-linked dominant
Onset: Infancy, Neonatal

Similar variants

CASK p.Thr548fs Pathogenic/Likely pathogenic ★★ same condition
CASK c.116_117delCA Pathogenic ★ same condition
CASK c.173-1145_278+7387del Likely pathogenic ★ same condition
CASK p.Arg613fs Likely pathogenic ★ same condition
CASK p.Asp98fs Pathogenic ★ same condition
CASK p.Cys205fs Likely pathogenic ★ same condition
CASK p.Ile649fs Likely pathogenic ★ same condition
CASK p.Leu604fs 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/cask-p-val292del (accessed [today's date]).

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