ADAMTSL4 p.Ser488=
c.1464G>A · rs587675749 · VCV292533
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
2
ectopia lentis et pupillae
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.014 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ1.00 | acceptor gain · deltas |
| Pangolin | Δ0.87 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.095 | GERP -0.61, phastCons 0.69 |
| Overall | ||
| CADD | 23.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,058 alleles
Filtering AF
0.00661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.00291%
47/1,614,080 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,058 |
| Admixed American | 0.0133% | 7,502 |
| South Asian | 0.00439% | 22,770 |
| European (non-Finnish) | 0.0028% | 35,758 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,498 |
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.Ser488=
- Coding
- c.1464G>A
- MANE Select
- NM_019032
- dbSNP
- rs587675749
- Type
- single nucleotide variant
- Location
- chr1:150556254 (GRCh38)
- Gene constraint
- LOEUF 0.92 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.18
Similar variants
- ADAMTSL4 p.Ser488Leu Uncertain significance ★★ ⚠ same residue
- ADAMTSL4 c.2178-2A>G Likely pathogenic ★★ same condition
- ADAMTSL4 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
- ADAMTSL4 p.Arg141Ter Pathogenic ★★ same condition
- ADAMTSL4 p.Arg670Ter Pathogenic/Likely pathogenic ★★ same condition
- ADAMTSL4 p.Arg746His Pathogenic ★★ same condition
- ADAMTSL4 p.Arg865His Pathogenic/Likely pathogenic ★★ same condition
- ADAMTSL4 p.Cys799Ter Pathogenic ★★ 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/adamtsl4-p-ser488 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown