CASK c.172+277del
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.85%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +277 | deep intronic (+277 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.28 | GERP -2.5 |
| Non-coding constraint | — | not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained |
| Overall | ||
| CADD | 1.76 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.85%
African / African-American · 553/29,834 alleles
Filtering AF
1.73%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.68%
Overall
0.562%
608/108,208 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.85% | 54 |
| Remaining individualsnot grpmax-eligible | 0.742% | 135 |
| Admixed American | 0.404% | 248 |
| South Asian | 0.0396% | 2,524 |
| European (non-Finnish) | 0.00386% | 25,891 |
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
- Coding
- c.172+277del
- MANE Select
- NM_001367721
- dbSNP
- rs751945206
- Type
- Deletion
- Location
- chrX:41852838 (GRCh38)
- Structure
- AlphaFold pLDDT 79.45 · 22 PDB
Similar variants
- CASK p.Thr548fs Pathogenic/Likely pathogenic ★★ same type
- CASK p.Val292del Likely pathogenic ★★ same type
- CASK c.1504-6del Benign/Likely benign ★★ same type
- CASK c.1669-6del Benign/Likely benign ★★ same type
- CASK c.2521-11del Benign ★★ same type
- CASK c.533-99_533-84del Benign ★★ same type
- CASK c.116_117delCA Pathogenic ★ same type
- CASK c.1504-2_1504-1del Likely pathogenic ★ same type
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-c-172-plus-277del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown