CYLD p.Arg235Ter
c.703A>T · VCV4764306
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
CYLD-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 4 of 19 |
| Splicing | ||
| SpliceAI | Δ0.20 | donor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP -0.24, phastCons 1 |
| Overall | ||
| CADD | 36.0 | 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.Arg235Ter
- Coding
- c.703A>T
- MANE Select
- NM_001378743
- Type
- single nucleotide variant
- Location
- chr16:50751802 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.06 · 6 PDB
- Residue 235
- the 'interaction with trip' region; a β-strand
Disease context
CYLD-related disorder
Similar variants
- 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
- CYLD p.Gln312Ter 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-arg235ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown