CYLD p.Gln716=
c.2148A>G · rs750038729 · VCV3025155
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00822%, nfe)
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 0.11 | GERP -2.8, phastCons 0.079 |
| Overall | ||
| CADD | 5.441 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00822%
European (non-Finnish) · 97/1,179,838 alleles
Filtering AF
0.00689%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00633%
Overall
0.00638%
103/1,613,758 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00822% | 12,163 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,233 |
| East Asian | 0.00223% | 44,828 |
| South Asian | 0.0022% | 45,541 |
| African / African-American | 0.00133% | 74,930 |
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.Gln716=
- Coding
- c.2148A>G
- MANE Select
- NM_001378743
- dbSNP
- rs750038729
- Type
- single nucleotide variant
- Location
- chr16:50791597 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.06 · 6 PDB
- Residue 716
- the usp domain
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-gln716 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown