ADAMTSL2 p.Phe326=
c.978C>T · VCV4853298
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0412%, 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 -7.8 | GERP -3.3 |
| Overall | ||
| CADD | 5.113 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0412%
Admixed American · 22/53,344 alleles
Filtering AF
0.0279%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0235%
Overall
0.00621%
97/1,562,712 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0412% | 2,425 |
| Middle Eastern | 0.0334% | 2,991 |
| African / African-American | 0.0108% | 9,299 |
| Remaining individualsnot grpmax-eligible | 0.00822% | 12,163 |
| East Asian | 0.00697% | 14,352 |
| European (non-Finnish) | 0.00484% | 20,652 |
| South Asian | 0.00117% | 85,756 |
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.Phe326=
- Coding
- c.978C>T
- MANE Select
- NM_014694
- Type
- single nucleotide variant
- Location
- chr9:133554395 (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.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
- ADAMTSL2 c.-151+2T>C Uncertain significance ★★ same type
- ADAMTSL2 p.Arg128Gln 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/adamtsl2-p-phe326 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown