ADAMTSL2 p.Arg166=
c.498C>T · VCV4853172
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00833%, amr)
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 -6.8 | GERP -2.4 |
| Overall | ||
| CADD | 8.507 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00833%
Admixed American · 5/60,010 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00285%
46/1,613,718 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00833% | 12,002 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| European (non-Finnish) | 0.00305% | 32,779 |
| African / African-American | 0.00133% | 74,940 |
| South Asian | 0.0011% | 91,092 |
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.Arg166=
- Coding
- c.498C>T
- MANE Select
- NM_014694
- Type
- single nucleotide variant
- Location
- chr9:133540683 (GRCh38)
- Gene constraint
- LOEUF 0.679 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 67.10
Similar variants
- ADAMTSL2 p.Arg166His Uncertain significance ★★ ⚠ same residue
- ADAMTSL2 p.Arg166Cys Likely pathogenic ★ ⚠ same residue
- ADAMTSL2 p.Arg113Cys Likely pathogenic ★★ same type
- ADAMTSL2 p.Arg113His Likely pathogenic ★★ same type
- ADAMTSL2 p.Arg113Leu Likely pathogenic ★★ same type
- ADAMTSL2 p.Arg177Ter Pathogenic/Likely pathogenic ★★ same type
- ADAMTSL2 p.Arg240Ter Pathogenic/Likely pathogenic ★★ same type
- ADAMTSL2 p.Gln77Ter 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/adamtsl2-p-arg166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown