Is CASK p.Tyr708fs (c.2120dup) pathogenic?

CASK p.Tyr708fs (c.2120dup) is classified Pathogenic/Likely pathogenic in CASK (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-02-18). Absent from gnomAD; Associated with isolated cerebellar hypoplasia/agenesis.

What condition is associated with CASK p.Tyr708fs (c.2120dup)?

CASK p.Tyr708fs (c.2120dup) is associated with isolated cerebellar hypoplasia/agenesis, syndromic X-linked intellectual disability Najm type (ClinVar).

How common is CASK p.Tyr708fs (c.2120dup) in the general population?

CASK p.Tyr708fs (c.2120dup) is absent from gnomAD (gnomAD).

CASK p.Tyr708fs

c.2120dup · rs1569295677 · VCV632602

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

isolated cerebellar hypoplasia/agenesis

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 22 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP 1, 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.Tyr708fs
Coding: c.2120dup
MANE Select: NM_001367721
dbSNP: rs1569295677
Type: Duplication
Location: chrX:41542725 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 708: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); 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

isolated cerebellar hypoplasia/agenesis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: syndromic X-linked intellectual disability Najm type

Similar variants

CASK c.1315-4_1315-1dup Likely pathogenic ★ same condition
CASK p.Ala187fs Likely pathogenic ★ same condition
CASK p.Asn666fs Pathogenic ★ same condition
CASK p.Gly306fs Pathogenic ★ same condition
CASK p.Met186fs Pathogenic ★ same condition
CASK p.Pro329fs Likely pathogenic ★ same condition
CASK p.Ser172fs Likely pathogenic ★ same condition
CASK p.Ile524_His525insMetIle Uncertain significance ★ 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-tyr708fs (accessed [today's date]).

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