CYLD p.Leu640=
c.1920G>A · rs182210792 · VCV733826
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.065%, amr)
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 2.1 | GERP -0.65, phastCons 1 |
| Overall | ||
| CADD | 8.322 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.065%
Admixed American · 39/60,016 alleles
Filtering AF
0.0488%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0432%
Overall
0.0031%
50/1,613,370 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.065% | 1,539 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,942 |
| African / African-American | 0.00133% | 75,052 |
| European (non-Finnish) | 8.48e-05% | 1,179,773 |
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.Leu640=
- Coding
- c.1920G>A
- MANE Select
- NM_001378743
- dbSNP
- rs182210792
- Type
- single nucleotide variant
- Location
- chr16:50784422 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.06 · 6 PDB
- Residue 640
- the usp domain; an α-helix
Similar variants
- CYLD p.Leu640Pro 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-leu640 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown