CYLD p.Leu780=
c.2340A>G · rs758417671 · VCV3037023
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000773%, nfe)
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 2.1 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 6.656 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000773%
European (non-Finnish) · 8/1,035,042 alleles
Filtering AF
0.000332%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00024%
Overall
0.000553%
8/1,447,518 alleles · very rare
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.Leu780=
- Coding
- c.2340A>G
- MANE Select
- NM_001378743
- dbSNP
- rs758417671
- Type
- single nucleotide variant
- Location
- chr16:50792695 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.06 · 6 PDB
- Residue 780
- an α-helix; 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-leu780 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown