Is CASK p.Ala814= (c.2442G>A) pathogenic?

CASK p.Ala814= (c.2442G>A) is classified Benign/Likely benign in CASK (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.77%, sas); Associated with Inborn genetic diseases.

What condition is associated with CASK p.Ala814= (c.2442G>A)?

CASK p.Ala814= (c.2442G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CASK p.Ala814= (c.2442G>A) in the general population?

CASK p.Ala814= (c.2442G>A) is low-frequency (popmax 1.77%, sas) (gnomAD).

CASK p.Ala814=

c.2442G>A · rs141158465 · VCV158073

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.77%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.1	GERP -3.5
Overall
CADD	1.201	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.77% South Asian · 1,006/56,808 alleles

Filtering AF 1.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.64%

Overall 0.106% 1,282/1,209,563 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.77%	56
Remaining individualsnot grpmax-eligible	0.12%	835
European (non-Finnish)	0.0227%	4,407
Finnishnot grpmax-eligible	0.0172%	5,823
African / African-American	0.00699%	14,313
East Asian	0.00592%	16,890
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,034
Admixed American	0.00218%	45,790

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.Ala814=
Coding: c.2442G>A
MANE Select: NM_001367721
dbSNP: rs141158465
Type: single nucleotide variant
Location: chrX:41531085 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 814: 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; 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.Asn31Ser 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

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-ala814 (accessed [today's date]).

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