ADAMTSL4 p.Pro85=
c.255T>A · rs1570924460 · VCV797350
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0894%, nfe)
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 -0.12 | GERP -2.9, phastCons 0.059 |
| Overall | ||
| CADD | 5.342 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0894%
European (non-Finnish) · 890/995,624 alleles
Filtering AF
0.0845%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0825%
Overall
0.0716%
989/1,380,942 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0894% | 1,119 |
| Remaining individualsnot grpmax-eligible | 0.0582% | 1,719 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0478% | 2,093 |
| South Asian | 0.0299% | 3,340 |
| East Asian | 0.0239% | 4,189 |
| African / African-American | 0.019% | 5,252 |
| Middle Eastern | 0.0189% | 5,294 |
| Admixed American | 0.0106% | 9,411 |
| Finnishnot grpmax-eligible | 0.00376% | 26,588 |
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
- ADAMTSL4
- Protein
- p.Pro85=
- Coding
- c.255T>A
- MANE Select
- NM_019032
- dbSNP
- rs1570924460
- Type
- single nucleotide variant
- Location
- chr1:150553074 (GRCh38)
- Gene constraint
- LOEUF 0.92 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.18
- Residue 85
- the tsp type-1 1 domain; the 'disordered' region
Similar variants
- ADAMTSL4 c.2178-2A>G Likely pathogenic ★★ same type
- ADAMTSL4 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same type
- ADAMTSL4 p.Arg126Ter Pathogenic/Likely pathogenic ★★ same type
- ADAMTSL4 p.Arg141Ter Pathogenic ★★ same type
- ADAMTSL4 p.Arg309Ter Pathogenic ★★ same type
- ADAMTSL4 p.Arg670Ter Pathogenic/Likely pathogenic ★★ same type
- ADAMTSL4 p.Arg746His Pathogenic ★★ same type
- ADAMTSL4 p.Arg865His 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/adamtsl4-p-pro85 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown