ADAMTS10 p.Phe398=
c.1194C>T · rs782096562 · VCV893642
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, eas)
Conditions
1
Weill-Marchesani syndrome
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 Δ0.62 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.009 | GERP -4.1, phastCons 0.1 |
| Overall | ||
| CADD | 14.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
East Asian · 9/44,892 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00779%
Overall
0.00149%
24/1,613,712 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.02% | 4,988 |
| Admixed American | 0.00333% | 30,002 |
| European (non-Finnish) | 0.0011% | 90,771 |
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
- ADAMTS10
- Protein
- p.Phe398=
- Coding
- c.1194C>T
- MANE Select
- NM_030957
- dbSNP
- rs782096562
- Type
- single nucleotide variant
- Location
- chr19:8596216 (GRCh38)
- Gene constraint
- LOEUF 0.467 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.88
- Residue 398
- a disulfide bond; the peptidase m12b domain
Similar variants
- ADAMTS10 c.-99-3C>T Uncertain significance ★★ same condition
- ADAMTS10 p.Arg186Leu Uncertain significance ★★ ⚠ same condition
- ADAMTS10 p.Arg205Trp Uncertain significance ★★ ⚠ same condition
- ADAMTS10 p.Arg210Trp Uncertain significance ★★ ⚠ same condition
- ADAMTS10 p.Asn429Asp Uncertain significance ★★ ⚠ same condition
- ADAMTS10 p.Glu173Gly Uncertain significance ★★ ⚠ same condition
- ADAMTS10 p.Glu709Lys Uncertain significance ★★ ⚠ same condition
- ADAMTS10 p.Gly163Ser Uncertain significance ★★ ⚠ 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/adamts10-p-phe398 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown