Is CASK p.Asn598= (c.1794C>T) pathogenic?

CASK p.Asn598= (c.1794C>T) is classified Benign/Likely benign in CASK (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-13). Ultra-rare (popmax 0.03%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CASK p.Asn598= (c.1794C>T)?

CASK p.Asn598= (c.1794C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CASK p.Asn598= (c.1794C>T) in the general population?

CASK p.Asn598= (c.1794C>T) is ultra-rare (popmax 0.03%, nfe) (gnomAD).

CASK p.Asn598=

c.1794C>T · rs143991107 · VCV94375

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, nfe)

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 12	GERP 1.7, phastCons 1
Overall
CADD	10.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% European (non-Finnish) · 268/892,325 alleles

Filtering AF 0.027% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.0602% 726/1,206,876 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.651%	154
Ashkenazi Jewishnot grpmax-eligible	0.559%	179
Remaining individualsnot grpmax-eligible	0.0632%	1,583
European (non-Finnish)grpmax	0.03%	3,330
Admixed American	0.00219%	45,723
African / African-American	0.00175%	57,211

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn598=
Coding: c.1794C>T
MANE Select: NM_001367721
dbSNP: rs143991107
Type: single nucleotide variant
Location: chrX:41557044 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 598: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the 'required for interaction with nrxn1 (via c-terminal tail)' region; the 'disordered' region

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.Asn598Asp Uncertain significance ★ ⚠ same residue
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

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-asn598 (accessed [today's date]).

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