Is CASK c.2039+1del pathogenic?

CASK c.2039+1del 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 c.2039+1del?

CASK c.2039+1del is associated with syndromic X-linked intellectual disability Najm type (ClinVar).

How common is CASK c.2039+1del in the general population?

CASK c.2039+1del 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 c.2039+1del

rs2519751285 · VCV977820

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

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	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Non-coding constraint	—	not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained

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
Coding: c.2039+1del
MANE Select: NM_001367721
dbSNP: rs2519751285
Type: Deletion
Location: chrX:41553718 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB

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-c-2039-plus-1del (accessed [today's date]).

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