Is CASK p.Ile265fs (c.794_796delinsAG) pathogenic?

CASK p.Ile265fs (c.794796delinsAG) is classified Pathogenic in CASK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-07). No gnomAD frequency available for this variant; Associated with Developmental disorder.

What condition is associated with CASK p.Ile265fs (c.794_796delinsAG)?

CASK p.Ile265fs (c.794_796delinsAG) is associated with Developmental disorder (ClinVar).

How common is CASK p.Ile265fs (c.794_796delinsAG) in the general population?

CASK p.Ile265fs (c.794_796delinsAG) is no gnomAD frequency available for this variant (gnomAD).

CASK p.Ile265fs

c.794_796delinsAG · rs2519199772 · VCV2429865

Pathogenic Single submitter

Classification

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

Developmental 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 8 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.3, 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.Ile265fs
Coding: c.794_796delinsAG
MANE Select: NM_001367721
dbSNP: rs2519199772
Type: Indel
Location: chrX:41660474 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 265: the protein kinase domain; 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

Developmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASK p.Ile265Phe Uncertain significance ★ ⚠ same residue
CASK c.2317+5G>A Pathogenic/Likely pathogenic ★★ same condition
CASK p.Ala166Asp Pathogenic ★ same condition
CASK p.Lys665Arg Likely benign ★ same condition
CASK c.2155+4_2155+6delinsA Uncertain significance ★★ same type
CASK c.2236+1delinsAT Likely pathogenic ★ same type
CASK p.Thr182_Pro183delinsProThrTer Pathogenic ★ same type
CASK p.Thr222fs Likely pathogenic ★ same type

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-ile265fs (accessed [today's date]).

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