CYLD p.Arg758Ter
c.2272C>T · rs121908388 · VCV5253
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
3
CYLD-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 16 of 19 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 41.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CYLD
- Protein
- p.Arg758Ter
- Coding
- c.2272C>T
- MANE Select
- NM_001378743
- dbSNP
- rs121908388
- Type
- single nucleotide variant
- Location
- chr16:50792627 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.06 · 6 PDB
- Residue 758
- the usp domain
Similar variants
- CYLD p.Arg758Gln Uncertain significance ★★ ⚠ same residue
- CYLD p.Arg235Ter Pathogenic/Likely pathogenic ★★ same condition
- CYLD p.Arg936Ter Pathogenic/Likely pathogenic ★★ same condition
- CYLD p.Lys767Ter Pathogenic ★★ same condition
- CYLD p.Ser371Ter Pathogenic ★★ same condition
- CYLD p.Ser839Ter Pathogenic/Likely pathogenic ★★ same condition
- CYLD p.Trp847Ter Pathogenic ★★ same condition
- CYLD c.*3229C>T 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/cyld-p-arg758ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown