Is CASK p.Pro329fs (c.984dup) pathogenic?

CASK p.Pro329fs (c.984dup) is classified Likely pathogenic in CASK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). Associated with syndromic X-linked intellectual disability Najm type.

What condition is associated with CASK p.Pro329fs (c.984dup)?

CASK p.Pro329fs (c.984dup) is associated with syndromic X-linked intellectual disability Najm type (ClinVar).

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.Pro329fs

c.984dup · VCV4855099

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.8	GERP 0.98, phastCons 1

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

Variant & gene context

Gene: CASK
Protein: p.Pro329fs
Coding: c.984dup
MANE Select: NM_001367721
Type: Duplication
Location: chrX:41626634 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 329: 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

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

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

Inheritance: X-linked dominant
Onset: Infancy, Neonatal

Similar variants

CASK c.1315-4_1315-1dup Likely pathogenic ★ same condition
CASK p.Ala187fs Likely pathogenic ★ same condition
CASK p.Asn666fs Pathogenic ★ same condition
CASK p.Gly306fs Pathogenic ★ same condition
CASK p.Met186fs Pathogenic ★ same condition
CASK p.Ser172fs Likely pathogenic ★ same condition
CASK p.Ile524_His525insMetIle Uncertain significance ★ same condition
CASK p.Pro329Thr Uncertain significance ★ ⚠ same residue

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-pro329fs (accessed [today's date]).

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