CYLD p.Thr412=
c.1236C>T · rs754746750 · VCV798323
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0227%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | acceptor loss, 26 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.5 | GERP -4.5 |
| Overall | ||
| CADD | 2.213 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0227%
African / African-American · 17/74,994 alleles
Filtering AF
0.0144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0118%
Overall
0.00273%
44/1,613,910 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0227% | 4,411 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,834 |
| East Asian | 0.00223% | 44,886 |
| European (non-Finnish) | 0.00186% | 53,636 |
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.Thr412=
- Coding
- c.1236C>T
- MANE Select
- NM_001378743
- dbSNP
- rs754746750
- Type
- single nucleotide variant
- Location
- chr16:50779762 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.06 · 6 PDB
- Residue 412
- the 'interaction with trip' region; the 'interaction with traf2' region
Similar variants
- CYLD p.Arg235Ter Pathogenic/Likely pathogenic ★★ same type
- CYLD p.Arg758Ter Pathogenic ★★ same type
- CYLD p.Arg936Ter Pathogenic/Likely pathogenic ★★ same type
- CYLD p.Lys767Ter Pathogenic ★★ same type
- CYLD p.Ser371Ter Pathogenic ★★ same type
- CYLD p.Ser839Ter Pathogenic/Likely pathogenic ★★ same type
- CYLD p.Trp847Ter Pathogenic ★★ same type
- CYLD c.*3229C>T Uncertain significance ★★ 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/cyld-p-thr412 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown