Is CASK p.Asp794Val (c.2381A>T) pathogenic?

CASK p.Asp794Val (c.2381A>T) is classified Uncertain significance in CASK (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-10). AlphaMissense: ambiguous (0.5024); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with CASK p.Asp794Val (c.2381A>T)?

CASK p.Asp794Val (c.2381A>T) is associated with intellectual disability (ClinVar).

How common is CASK p.Asp794Val (c.2381A>T) in the general population?

CASK p.Asp794Val (c.2381A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CASK p.Asp794Val (c.2381A>T)?

AlphaMissense predicts ambiguous (score 0.5024) — an in-silico prediction, not a clinical call.

CASK p.Asp794Val

c.2381A>T · rs2064797651 · VCV981294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5024 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.5024	ambiguous
REVEL	0.708	pathogenic-leaning
SaProt	LLR -12.62	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 22 kb · p 7.7e-05 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Asp794Val
Coding: c.2381A>T
MANE Select: NM_001367721
dbSNP: rs2064797651
Type: single nucleotide variant
Location: chrX:41531146 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 794: 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; an α-helix

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASK p.Asp794Glu Uncertain significance ★ ⚠ same residue
CASK p.Arg639Ter Pathogenic ★★ same condition
CASK p.Gly164Arg Likely pathogenic ★ same condition
CASK p.Phe163Leu Likely pathogenic ★ same condition
CASK p.Gly206Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
CASK p.Met501Val Uncertain significance ★ ⚠ same condition
CASK p.Ala342Val Uncertain significance ⚠ same condition
CASK p.Val292del 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-asp794val (accessed [today's date]).

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