ADAMTS18 p.Thr488=
c.1464A>C · rs376633413 · VCV1169761
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.552%, sas)
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 -0.037 | GERP -2, phastCons 0.91 |
| Overall | ||
| CADD | 2.829 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.552%
South Asian · 503/91,088 alleles
Filtering AF
0.512%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.497%
Overall
0.0356%
575/1,614,170 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.552% | 181 |
| Middle Eastern | 0.0825% | 1,212 |
| Remaining individualsnot grpmax-eligible | 0.0608% | 1,645 |
| African / African-American | 0.00799% | 12,508 |
| Admixed American | 0.00333% | 30,000 |
| East Asian | 0.00223% | 44,874 |
| European (non-Finnish) | 0.00169% | 59,002 |
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.Thr488=
- Coding
- c.1464A>C
- MANE Select
- NM_199355
- dbSNP
- rs376633413
- Type
- single nucleotide variant
- Location
- chr16:77353883 (GRCh38)
- Gene constraint
- LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.83
- Residue 488
- a disulfide bond; the peptidase m12b domain
Similar variants
- 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
- ADAMTS18 p.Arg88Ter 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-thr488 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown