Is CASK p.Glu812Gln (c.2434G>C) pathogenic?

CASK p.Glu812Gln (c.2434G>C) is classified Uncertain significance in CASK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.8976); Absent from gnomAD v4.1; Associated with FG syndrome 4.

What condition is associated with CASK p.Glu812Gln (c.2434G>C)?

CASK p.Glu812Gln (c.2434G>C) is associated with FG syndrome 4 (ClinVar).

How common is CASK p.Glu812Gln (c.2434G>C) in the general population?

CASK p.Glu812Gln (c.2434G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CASK p.Glu812Gln (c.2434G>C)?

AlphaMissense predicts likely pathogenic (score 0.8976) — an in-silico prediction, not a clinical call.

CASK p.Glu812Gln

c.2434G>C · rs1235769310 · VCV1330235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8976 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FG syndrome 4

Computational evidence

Protein change
AlphaMissense	0.8976	likely pathogenic
REVEL	0.155	moderately benign-leaning
SaProt	LLR -10.96	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP -0.3, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 22 kb · p 7.7e-05 · regional, not allelic
Overall
CADD	29.7	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.Glu812Gln
Coding: c.2434G>C
MANE Select: NM_001367721
dbSNP: rs1235769310
Type: single nucleotide variant
Location: chrX:41531093 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 812: 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

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

Disease context

FG syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASK p.Glu812Lys Uncertain significance ★ ⚠ same residue
CASK c.2317+5G>A Pathogenic/Likely pathogenic ★★ same condition
CASK c.2521-2A>G Pathogenic/Likely pathogenic ★★ same condition
CASK c.59+2T>C Pathogenic/Likely pathogenic ★★ same condition
CASK p.Arg28Ter Pathogenic ★★ same condition
CASK p.Arg489Gln Pathogenic/Likely pathogenic ★★ same condition
CASK p.Arg613Ter Pathogenic/Likely pathogenic ★★ same condition
CASK p.Glu102Gly Pathogenic/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-glu812gln (accessed [today's date]).

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