Is CASK p.Thr893fs (c.2678_2679del) pathogenic?

CASK p.Thr893fs (c.26782679del) is classified Likely pathogenic in CASK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-12). No gnomAD frequency available for this variant; Associated with syndromic X-linked intellectual disability Najm type.

What condition is associated with CASK p.Thr893fs (c.2678_2679del)?

CASK p.Thr893fs (c.2678_2679del) is associated with syndromic X-linked intellectual disability Najm type (ClinVar).

How common is CASK p.Thr893fs (c.2678_2679del) in the general population?

CASK p.Thr893fs (c.2678_2679del) is no gnomAD frequency available for this variant (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.Thr893fs

c.2678_2679del · rs2519652117 · VCV2502362

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

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	escapes	premature termination codon in the last exon (27 of 27) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, 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.Thr893fs
Coding: c.2678_2679del
MANE Select: NM_001367721
dbSNP: rs2519652117
Type: Microsatellite
Location: chrX:41520522 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 893: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the guanylate kinase-like domain; the 'required for interaction with nrxn1 (via c-terminal tail)' region; a β-strand

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.Asp95fs Pathogenic ★★ same condition
CASK c.278+2_278+3del Pathogenic ★ same condition
CASK p.Glu849fs Pathogenic ★ same condition
CASK p.Ile755fs Likely pathogenic ★ same condition
CASK p.Thr893Lys Uncertain significance ★ same residue
CASK c.1015+1G>A Pathogenic ★★ same condition
CASK c.1315-1G>A Pathogenic/Likely pathogenic ★★ same condition
CASK c.2317+1G>A Pathogenic/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-thr893fs (accessed [today's date]).

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