Is CASK p.His811= (c.2433C>T) pathogenic?

CASK p.His811= (c.2433C>T) is classified Benign/Likely benign in CASK (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-13). Ultra-rare (popmax 0.0351%, nfe); Associated with Intellectual disability, CASK-related, X-linked.

What condition is associated with CASK p.His811= (c.2433C>T)?

CASK p.His811= (c.2433C>T) is associated with Intellectual disability, CASK-related, X-linked (ClinVar).

How common is CASK p.His811= (c.2433C>T) in the general population?

CASK p.His811= (c.2433C>T) is ultra-rare (popmax 0.0351%, nfe) (gnomAD).

CASK p.His811=

c.2433C>T · rs371990384 · VCV388002

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0351%, nfe)

Conditions

Intellectual disability, CASK-related, X-linked

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 -8.2	GERP -3.5
Overall
CADD	0.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0351% European (non-Finnish) · 314/893,840 alleles

Filtering AF 0.0319% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0306%

Overall 0.0278% 336/1,208,618 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0351%	2,847
Remaining individualsnot grpmax-eligible	0.0252%	3,964
Middle Eastern	0.023%	4,345
East Asian	0.0118%	8,445
Admixed American	0.00437%	22,886
African / African-American	0.00349%	28,626
South Asian	0.00176%	56,788

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.His811=
Coding: c.2433C>T
MANE Select: NM_001367721
dbSNP: rs371990384
Type: single nucleotide variant
Location: chrX:41531094 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 811: 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

Intellectual disability, CASK-related, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASK p.Arg489Gln Pathogenic/Likely pathogenic ★★ same condition
CASK p.Ala359Val Uncertain significance ★★ ⚠ same condition
CASK p.Ala833Thr Uncertain significance ★★ ⚠ same condition
CASK p.Arg130Cys Uncertain significance ★★ ⚠ same condition
CASK p.Arg572His Uncertain significance ★★ ⚠ same condition
CASK p.Arg61Trp Uncertain significance ★★ ⚠ same condition
CASK p.Asp424Gly Uncertain significance ★★ ⚠ same condition
CASK p.Asp445Asn 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-his811 (accessed [today's date]).

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