CYLD p.His825=
c.2475C>T · rs918661035 · VCV3034171
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
CYLD-related disorder
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 0.58 | GERP -0.31, phastCons 1 |
| Overall | ||
| CADD | 7.368 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,888 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00105%
17/1,613,852 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,888 |
| European (non-Finnish) | 0.00136% | 73,745 |
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
- CYLD
- Protein
- p.His825=
- Coding
- c.2475C>T
- MANE Select
- NM_001378743
- dbSNP
- rs918661035
- Type
- single nucleotide variant
- Location
- chr16:50794217 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.06 · 6 PDB
- Residue 825
- the 'b-box' region; a binding site; the usp domain
Disease context
CYLD-related disorder
Similar variants
- CYLD p.Arg235Ter Pathogenic/Likely pathogenic ★★ same condition
- CYLD p.Arg758Ter Pathogenic ★★ same condition
- CYLD p.Arg936Ter Pathogenic/Likely pathogenic ★★ same condition
- CYLD p.Ser839Ter Pathogenic/Likely pathogenic ★★ same condition
- CYLD p.Trp847Ter Pathogenic ★★ same condition
- CYLD c.1684+3A>G Likely pathogenic ★ same condition
- CYLD c.2108+2T>C Pathogenic ★ same condition
- CYLD c.2350+5G>A Likely pathogenic ★ 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/cyld-p-his825 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown