ADAMTSL2 p.Pro106=
c.318G>A · rs191009072 · VCV976603
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.615%, eas)
Conditions
1
geleophysic dysplasia 1
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 -0.84 | GERP -3 |
| Overall | ||
| CADD | 9.531 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.615%
East Asian · 233/37,874 alleles
Filtering AF
0.55%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.525%
Overall
0.0241%
364/1,507,780 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.615% | 163 |
| South Asian | 0.044% | 2,275 |
| Remaining individualsnot grpmax-eligible | 0.0426% | 2,348 |
| Middle Eastern | 0.0344% | 2,909 |
| Admixed American | 0.0189% | 5,304 |
| African / African-American | 0.00609% | 16,428 |
| European (non-Finnish) | 0.00488% | 20,484 |
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
- ADAMTSL2
- Protein
- p.Pro106=
- Coding
- c.318G>A
- MANE Select
- NM_014694
- dbSNP
- rs191009072
- Type
- single nucleotide variant
- Location
- chr9:133539779 (GRCh38)
- Gene constraint
- LOEUF 0.679 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 67.10
- Residue 106
- the tsp type-1 1 domain
Similar variants
- ADAMTSL2 p.Arg113Cys Likely pathogenic ★★ same condition
- ADAMTSL2 p.Arg113His Likely pathogenic ★★ same condition
- ADAMTSL2 p.Arg113Leu Likely pathogenic ★★ same condition
- ADAMTSL2 p.Arg177Ter Pathogenic/Likely pathogenic ★★ same condition
- ADAMTSL2 p.Arg425Gln Uncertain significance ★★ ⚠ same condition
- ADAMTSL2 p.Arg4Thr Uncertain significance ★★ ⚠ same condition
- ADAMTSL2 p.Arg681Gln Uncertain significance ★★ ⚠ same condition
- ADAMTSL2 p.Glu327Lys Uncertain significance ★★ ⚠ same condition
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/adamtsl2-p-pro106 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown