ADAMTS13 p.Ser447=
c.1341G>A · rs587602874 · VCV365544
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0251%, eas)
Conditions
1
congenital thrombotic thrombocytopenic purpura
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.51 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -4.3 |
| Overall | ||
| CADD | 0.664 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0251%
East Asian · 11/43,812 alleles
Filtering AF
0.014%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0109%
Overall
0.00441%
70/1,586,156 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0251% | 3,983 |
| Admixed American | 0.0233% | 4,288 |
| Middle Eastern | 0.0167% | 5,996 |
| African / African-American | 0.0109% | 9,158 |
| Remaining individualsnot grpmax-eligible | 0.00488% | 20,503 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00345% | 29,026 |
| South Asian | 0.00343% | 29,113 |
| European (non-Finnish) | 0.00257% | 38,945 |
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.Ser447=
- Coding
- c.1341G>A
- MANE Select
- NM_139027
- dbSNP
- rs587602874
- Type
- single nucleotide variant
- Location
- chr9:133436861 (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 447
- the 'cysteine-rich' region; an α-helix
Similar variants
- ADAMTS13 p.Ser447Leu Uncertain significance ★ ⚠ same residue
- ADAMTS13 c.1705+1G>A Likely pathogenic ★★ same condition
- ADAMTS13 c.330+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ADAMTS13 p.Ala596Val Pathogenic ★★ same condition
- ADAMTS13 p.Ala690Thr Likely pathogenic ★★ ⚠ same condition
- ADAMTS13 p.Arg102Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ADAMTS13 p.Arg102His Likely pathogenic ★★ ⚠ same condition
- ADAMTS13 p.Arg1060Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
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-ser447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown