Is CASK p.Asn31Ser (c.92A>G) pathogenic?

CASK p.Asn31Ser (c.92A>G) is classified Uncertain significance in CASK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-11). AlphaMissense: likely benign (0.0994); Very rare (popmax 0.00176%, sas); Associated with Inborn genetic diseases.

What condition is associated with CASK p.Asn31Ser (c.92A>G)?

CASK p.Asn31Ser (c.92A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CASK p.Asn31Ser (c.92A>G) in the general population?

CASK p.Asn31Ser (c.92A>G) is very rare (popmax 0.00176%, sas) (gnomAD).

What do computational predictors say about CASK p.Asn31Ser (c.92A>G)?

AlphaMissense predicts likely benign (score 0.0994) — an in-silico prediction, not a clinical call.

CASK p.Asn31Ser

c.92A>G · rs2519892738 · VCV1766470

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00176%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0994	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -10.93	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.9, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 286 kb · p 1e-25 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 0.00176% South Asian · 1/56,808 alleles

Overall 9.16e-05% 1/1,091,676 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CASK
Protein: p.Asn31Ser
Coding: c.92A>G
MANE Select: NM_001367721
dbSNP: rs2519892738
Type: single nucleotide variant
Location: chrX:41853195 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 31: the protein kinase domain; a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASK p.Ala300Thr Uncertain significance ★★ ⚠ same condition
CASK p.Arg560Trp Uncertain significance ★★ ⚠ same condition
CASK p.Arg766Trp Uncertain significance ★★ ⚠ same condition
CASK p.Asp330Gly Uncertain significance ★★ ⚠ same condition
CASK p.Asp498Gly Uncertain significance ★★ ⚠ same condition
CASK p.Glu662Asp Uncertain significance ★★ ⚠ same condition
CASK p.Gly21Asp Uncertain significance ★★ ⚠ same condition
CASK p.Gly221Arg Uncertain significance ★★ ⚠ 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-asn31ser (accessed [today's date]).

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