Is CASK p.Tyr419fs (c.1256del) pathogenic?

CASK p.Tyr419fs (c.1256del) is classified Likely pathogenic in CASK (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD; Associated with syndromic X-linked intellectual disability Najm type.

What condition is associated with CASK p.Tyr419fs (c.1256del)?

CASK p.Tyr419fs (c.1256del) is associated with syndromic X-linked intellectual disability Najm type (ClinVar).

How common is CASK p.Tyr419fs (c.1256del) in the general population?

CASK p.Tyr419fs (c.1256del) 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.Tyr419fs

c.1256del · rs2519844888 · VCV977902

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.8	GERP 0.45, 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: CASK
Protein: p.Tyr419fs
Coding: c.1256del
MANE Select: NM_001367721
dbSNP: rs2519844888
Type: Deletion
Location: chrX:41586965 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 419: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the l27 2 domain

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 p.Thr548fs Pathogenic/Likely pathogenic ★★ same condition
CASK p.Val292del 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

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-tyr419fs (accessed [today's date]).

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