ADAMTS18 p.Asp447=
c.1341T>C · rs8059275 · VCV1168653
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 91.3%, eas) — too common for a highly-penetrant pathogenic allele
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 -1.3 | GERP -5.8 |
| Overall | ||
| CADD | 0.846 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
91.3%
East Asian · 40,962/44,844 alleles
Filtering AF
90.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 90.3%
Overall
86.5%
1,395,843/1,613,832 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 91.3% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 91.3% | 1 |
| Amishnot grpmax-eligible | 91.1% | 1 |
| African / African-American | 89.3% | 1 |
| South Asian | 87.1% | 1 |
| Remaining individualsnot grpmax-eligible | 87% | 1 |
| European (non-Finnish) | 86.4% | 1 |
| Admixed American | 85.8% | 1 |
| Middle Eastern | 81.9% | 1 |
| Finnishnot grpmax-eligible | 78.1% | 1 |
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
- ADAMTS18
- Protein
- p.Asp447=
- Coding
- c.1341T>C
- MANE Select
- NM_199355
- dbSNP
- rs8059275
- Type
- single nucleotide variant
- Location
- chr16:77356059 (GRCh38)
- Gene constraint
- LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.83
- Residue 447
- a disulfide bond; the peptidase m12b domain
Similar variants
- ADAMTS18 p.Asp447Asn Uncertain significance ★ ⚠ same residue
- ADAMTS18 c.3006+1G>A Pathogenic/Likely pathogenic ★★ same type
- ADAMTS18 c.3007-1G>C Likely pathogenic ★★ same type
- ADAMTS18 p.Arg1009Ter Pathogenic/Likely pathogenic ★★ same type
- ADAMTS18 p.Arg1094Ter Pathogenic/Likely pathogenic ★★ same type
- ADAMTS18 p.Arg172Ter Pathogenic/Likely pathogenic ★★ same type
- ADAMTS18 p.Arg418Ter Pathogenic/Likely pathogenic ★★ same type
- ADAMTS18 p.Arg548Ter Pathogenic/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/adamts18-p-asp447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown