Is CASK p.Ala342Val (c.1025C>T) pathogenic?

CASK p.Ala342Val (c.1025C>T) is classified Uncertain significance in CASK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-01). AlphaMissense: ambiguous (0.4969); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with CASK p.Ala342Val (c.1025C>T)?

CASK p.Ala342Val (c.1025C>T) is associated with intellectual disability (ClinVar).

How common is CASK p.Ala342Val (c.1025C>T) in the general population?

CASK p.Ala342Val (c.1025C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CASK p.Ala342Val (c.1025C>T)?

AlphaMissense predicts ambiguous (score 0.4969) — an in-silico prediction, not a clinical call.

CASK p.Ala342Val

c.1025C>T · rs2066303451 · VCV975506

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4969 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,197,218)

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.4969	ambiguous
REVEL	0.311	indeterminate
SaProt	LLR -6.40	tolerated
Splicing
SpliceAI	Δ0.20	acceptor loss · deltas
Pangolin	Δ0.21	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 77 kb · p 1.9e-13 · regional, not allelic
Overall
CADD	31.0	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

No allele count reported in gnomAD v4.1 (AN 1,197,218). 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.Ala342Val
Coding: c.1025C>T
MANE Select: NM_001367721
dbSNP: rs2066303451
Type: single nucleotide variant
Location: chrX:41622625 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 342: 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

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

Similar variants

CASK p.Ala342= Likely benign ★ same residue
CASK p.Arg639Ter Pathogenic ★★ same condition
CASK p.Gly164Arg Likely pathogenic ★ same condition
CASK p.Phe163Leu Likely pathogenic ★ same condition
CASK p.Asp794Val Uncertain significance ★ ⚠ same condition
CASK p.Gly206Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
CASK p.Met501Val 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-ala342val (accessed [today's date]).

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