ADAMTS20 p.Ser755Phe
c.2264C>T · VCV3490792
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00892%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.457 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 198 kb · p 0.2 · regional, not allelic |
| Overall | ||
| CADD | 29.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00892%
East Asian · 4/44,834 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.00089%
13/1,460,146 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00892% | 11,209 |
| European (non-Finnish) | 0.000763% | 130,986 |
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
- ADAMTS20
- Protein
- p.Ser755Phe
- Coding
- c.2264C>T
- MANE Select
- NM_025003
- Type
- single nucleotide variant
- Location
- chr12:43443817 (GRCh38)
- Gene constraint
- LOEUF 0.947 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.35
- Residue 755
- the 'spacer' region
Similar variants
- ADAMTS20 p.His183Leu Uncertain significance ★★ same type
- ADAMTS20 p.Glu915Asp Benign ★★ same type
- ADAMTS20 p.Gly985= Benign ★★ same type
- ADAMTS20 p.Ala102Thr Uncertain significance ★ same type
- ADAMTS20 p.Ala1479Thr Uncertain significance ★ same type
- ADAMTS20 p.Ala1700Ser Uncertain significance ★ same type
- ADAMTS20 p.Ala1797Ser Uncertain significance ★ same type
- ADAMTS20 p.Ala431Thr Uncertain significance ★ 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/adamts20-p-ser755phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown