ADAMTS18 p.Ser698=
c.2094C>T · rs375521024 · VCV1102696
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0822%, mid)
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 Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.5 | GERP -3.9 |
| Overall | ||
| CADD | 5.357 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0822%
Middle Eastern · 5/6,084 alleles
Filtering AF
0.0323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.021%
Overall
0.0122%
197/1,613,646 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0822% | 1,217 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,165 |
| Admixed American | 0.0217% | 4,612 |
| European (non-Finnish) | 0.0131% | 7,662 |
| African / African-American | 0.00668% | 14,961 |
| South Asian | 0.00439% | 22,770 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,602 |
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.Ser698=
- Coding
- c.2094C>T
- MANE Select
- NM_199355
- dbSNP
- rs375521024
- Type
- single nucleotide variant
- Location
- chr16:77322405 (GRCh38)
- Gene constraint
- LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.83
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-ser698 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown