ADAMTSL4 p.Ala666=
c.1998G>A · rs374312050 · VCV1589203
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0077%, sas)
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 -0.24 | GERP -4.1, phastCons 0.002 |
| Overall | ||
| CADD | 12.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0077%
South Asian · 7/90,866 alleles
Filtering AF
0.00563%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.00608%
98/1,612,204 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0077% | 12,981 |
| European (non-Finnish) | 0.00687% | 14,564 |
| East Asian | 0.00669% | 14,947 |
| Finnishnot grpmax-eligible | 0.0063% | 15,869 |
| Admixed American | 0.00167% | 59,832 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,412 |
| African / African-American | 0.00134% | 74,856 |
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.Ala666=
- Coding
- c.1998G>A
- MANE Select
- NM_019032
- dbSNP
- rs374312050
- Type
- single nucleotide variant
- Location
- chr1:150557286 (GRCh38)
- Gene constraint
- LOEUF 0.92 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.18
Similar variants
- ADAMTSL4 p.Ala666Val Uncertain significance ★★ ⚠ same residue
- 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
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-ala666 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown