ADAMTSL4 p.Pro652=
c.1956C>T · rs77184517 · VCV743615
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.189%, afr)
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 -16 | GERP -4.1 |
| Overall | ||
| CADD | 1.711 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.189%
African / African-American · 142/74,980 alleles
Filtering AF
0.164%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.154%
Overall
0.0121%
195/1,611,042 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.189% | 528 |
| Admixed American | 0.0401% | 2,495 |
| Remaining individualsnot grpmax-eligible | 0.0273% | 3,664 |
| Middle Eastern | 0.0175% | 5,702 |
| East Asian | 0.0067% | 14,924 |
| South Asian | 0.0011% | 90,824 |
| European (non-Finnish) | 0.000594% | 168,469 |
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.Pro652=
- Coding
- c.1956C>T
- MANE Select
- NM_019032
- dbSNP
- rs77184517
- Type
- single nucleotide variant
- Location
- chr1:150557244 (GRCh38)
- Gene constraint
- LOEUF 0.92 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.18
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-pro652 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown