CYLD p.Gln403=
c.1209G>A · rs371382898 · VCV741063
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00407%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.41 | acceptor loss, 1 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.059 | GERP -3.1, phastCons 0.36 |
| Overall | ||
| CADD | 1.302 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00407%
European (non-Finnish) · 48/1,179,890 alleles
Filtering AF
0.00315%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00279%
Overall
0.00316%
51/1,613,450 alleles · very rare
exomes 46/1,461,750 · genomes 5/151,700 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00407% | 24,581 |
| African / African-American | 0.00268% | 37,383 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,470 |
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.Gln403=
- Coding
- c.1209G>A
- MANE Select
- NM_001378743
- dbSNP
- rs371382898
- Type
- single nucleotide variant
- Location
- chr16:50779735 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.06 · 6 PDB
- Residue 403
- the 'interaction with trip' region; the 'disordered' region; the 'interaction with traf2' region
Similar variants
- CYLD p.Gln403Pro Uncertain significance ★ ⚠ same residue
- 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
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-gln403 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown