Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 11 submitters
gnomAD v4.1
Common
common (popmax 36.8%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
Ehlers-Danlos syndrome, dermatosparaxis type
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 -3.7 | GERP -3.8 |
| Overall | ||
| CADD | 7.882 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
36.8%
East Asian · 16,504/44,856 alleles
Filtering AF
36.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 36.1%
Overall
24.4%
393,635/1,612,754 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 36.8% | 3 |
| Admixed American | 33% | 3 |
| Amishnot grpmax-eligible | 32.5% | 3 |
| South Asian | 30.6% | 3 |
| Finnishnot grpmax-eligible | 29.3% | 3 |
| Middle Eastern | 27.6% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 24.7% | 4 |
| Remaining individualsnot grpmax-eligible | 24% | 4 |
| European (non-Finnish) | 23.8% | 4 |
| African / African-American | 7.29% | 14 |
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
- ADAMTS2
- Protein
- p.Asp398=
- Coding
- c.1194C>T
- MANE Select
- NM_014244
- dbSNP
- rs2278221
- Type
- single nucleotide variant
- Location
- chr5:179154858 (GRCh38)
- Gene constraint
- LOEUF 0.568 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.59
- Residue 398
- a disulfide bond; the peptidase m12b domain
Disease context
Ehlers-Danlos syndrome, dermatosparaxis type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Dermatosparaxis Ehlers-Danlos syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- ADAMTS2 c.2085+1G>T Likely pathogenic ★★ same condition
- ADAMTS2 c.3088+1G>A Likely pathogenic ★★ same condition
- ADAMTS2 c.688+1G>A Likely pathogenic ★★ same condition
- ADAMTS2 c.688+2T>C Likely pathogenic ★★ same condition
- ADAMTS2 p.Arg1030Ter Pathogenic/Likely pathogenic ★★ same condition
- ADAMTS2 p.Arg980Ter Pathogenic/Likely pathogenic ★★ same condition
- ADAMTS2 p.Cys659Ter Pathogenic/Likely pathogenic ★★ same condition
- ADAMTS2 p.Gln225Ter 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/adamts2-p-asp398 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown