Is CASK p.Thr548fs (c.1641_1644del) pathogenic?

CASK p.Thr548fs (c.16411644del) is classified Pathogenic/Likely pathogenic in CASK (ClinVar, Multiple submitters, 6 submitters; last evaluated 2022-05-22). Absent from gnomAD; Associated with CASK-related disorder.

What condition is associated with CASK p.Thr548fs (c.1641_1644del)?

CASK p.Thr548fs (c.1641_1644del) is associated with CASK-related disorder, syndromic X-linked intellectual disability Najm type (ClinVar).

How common is CASK p.Thr548fs (c.1641_1644del) in the general population?

CASK p.Thr548fs (c.1641_1644del) is absent from gnomAD (gnomAD).

CASK p.Thr548fs

c.1641_1644del · rs1569306724 · VCV570810

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

CASK-related disorder

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 17 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	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.Thr548fs
Coding: c.1641_1644del
MANE Select: NM_001367721
dbSNP: rs1569306724
Type: Deletion
Location: chrX:41561583 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 548: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the pdz domain; the 'required for interaction with nrxn1 (via c-terminal tail)' region

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

Disease context

CASK-related disorder

Also linked: syndromic X-linked intellectual disability Najm type

Similar variants

CASK p.Val292del Likely pathogenic ★★ same condition
CASK c.116_117delCA Pathogenic ★ same condition
CASK c.1504-2_1504-1del Likely pathogenic ★ same condition
CASK c.173-1145_278+7387del Likely pathogenic ★ same condition
CASK p.Ala814fs Likely pathogenic ★ same condition
CASK p.Arg613fs Likely pathogenic ★ same condition
CASK p.Asp98fs Pathogenic ★ same condition
CASK p.Cys205fs 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-thr548fs (accessed [today's date]).

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