Is CASK p.Glu102Gly (c.305A>G) pathogenic?

CASK p.Glu102Gly (c.305A>G) is classified Pathogenic/Likely pathogenic in CASK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-10-19). AlphaMissense: likely pathogenic (0.9985); Absent from gnomAD v4.1; Associated with FG syndrome 4.

What condition is associated with CASK p.Glu102Gly (c.305A>G)?

CASK p.Glu102Gly (c.305A>G) is associated with FG syndrome 4 (ClinVar).

How common is CASK p.Glu102Gly (c.305A>G) in the general population?

CASK p.Glu102Gly (c.305A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CASK p.Glu102Gly (c.305A>G)?

AlphaMissense predicts likely pathogenic (score 0.9985) — an in-silico prediction, not a clinical call.

CASK p.Glu102Gly

c.305A>G · rs1569429756 · VCV575647

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9985 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,202,427)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

FG syndrome 4

Computational evidence

Protein change
AlphaMissense	0.9985	likely pathogenic ✓ concordant with ClinVar · top 9% in CASK
REVEL	0.635	indeterminate
SaProt	LLR -14.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 286 kb · p 1e-25 · 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

No allele count reported in gnomAD v4.1 (AN 1,202,427). 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.Glu102Gly
Coding: c.305A>G
MANE Select: NM_001367721
dbSNP: rs1569429756
Type: single nucleotide variant
Location: chrX:41745575 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 102: the protein kinase domain; a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); an α-helix

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 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.Tyr282Ter Pathogenic ★★ same condition
CASK p.Tyr728Cys 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-glu102gly (accessed [today's date]).

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