Is CASK p.Gln494Ter (c.1480C>T) pathogenic?

CASK p.Gln494Ter (c.1480C>T) is classified Pathogenic/Likely pathogenic in CASK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-10-17). Absent from gnomAD v4.1; Associated with CASK-related disorder.

What condition is associated with CASK p.Gln494Ter (c.1480C>T)?

CASK p.Gln494Ter (c.1480C>T) is associated with CASK-related disorder (ClinVar).

How common is CASK p.Gln494Ter (c.1480C>T) in the general population?

CASK p.Gln494Ter (c.1480C>T) is absent from gnomAD v4.1 (gnomAD).

CASK p.Gln494Ter

c.1480C>T · rs1064796879 · VCV424249

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

CASK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 27
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.73, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CASK
Protein: p.Gln494Ter
Coding: c.1480C>T
MANE Select: NM_001367721
dbSNP: rs1064796879
Type: single nucleotide variant
Location: chrX:41578363 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 494: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the pdz domain; a β-strand; 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

Similar variants

CASK p.Arg28Ter Pathogenic ★★ same condition
CASK p.Arg489Trp Pathogenic/Likely pathogenic ★★ same condition
CASK c.1668+5G>A Likely pathogenic ★ same condition
CASK c.1737+2T>A Pathogenic ★ same condition
CASK c.708+2T>G Pathogenic ★ same condition
CASK c.709-1G>A Likely pathogenic ★ same condition
CASK p.Gln527Ter Pathogenic ★ same condition
CASK p.Gln840Ter 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-gln494ter (accessed [today's date]).

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