CYLD p.Asp178=
c.534C>T · rs377383082 · VCV2646513
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0132%, sas)
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 -0.73 | GERP -4.8, phastCons 0.022 |
| Overall | ||
| CADD | 8.084 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0132%
South Asian · 12/91,050 alleles
Filtering AF
0.00751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00593%
Overall
0.00167%
27/1,613,466 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0132% | 7,587 |
| East Asian | 0.00891% | 11,220 |
| European (non-Finnish) | 0.000932% | 107,245 |
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.Asp178=
- Coding
- c.534C>T
- MANE Select
- NM_001378743
- dbSNP
- rs377383082
- Type
- single nucleotide variant
- Location
- chr16:50751633 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.06 · 6 PDB
- Residue 178
- the cap-gly 1 domain; the 'interaction with trip' 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-asp178 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown