ADAMTS13 p.Cys366=
c.1098C>T · VCV4683456
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00834%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.453 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.19 | GERP -0.27, phastCons 0.96 |
| Overall | ||
| CADD | 3.458 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00834%
Admixed American · 5/59,982 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00031%
5/1,612,644 alleles · very rare
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
- ADAMTS13
- Protein
- p.Cys366=
- Coding
- c.1098C>T
- MANE Select
- NM_139027
- Type
- single nucleotide variant
- Location
- chr9:133433383 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 76.00 · 5 PDB
- Residue 366
- a β-strand; the disintegrin domain; a disulfide bond
Similar variants
- ADAMTS13 p.Cys366Tyr Likely pathogenic ★ same residue
- ADAMTS13 c.1705+1G>A Likely pathogenic ★★ same type
- ADAMTS13 c.3044+1G>A Pathogenic/Likely pathogenic ★★ same type
- ADAMTS13 c.330+1G>A Pathogenic/Likely pathogenic ★★ same type
- ADAMTS13 p.Ala596Val Pathogenic ★★ same type
- ADAMTS13 p.Ala690Thr Likely pathogenic ★★ ⚠ same type
- ADAMTS13 p.Arg102Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- ADAMTS13 p.Arg102His Likely 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/adamts13-p-cys366 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown