ADSL p.Ile424=
c.1272A>T · rs1057522571 · VCV386682
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00203%, nfe)
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 -0.15 | GERP -5, phastCons 0.011 |
| Overall | ||
| CADD | 6.501 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00203%
European (non-Finnish) · 24/1,179,992 alleles
Filtering AF
0.00138%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00116%
Overall
0.00164%
24/1,461,850 alleles · very rare
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
- ADSL
- Protein
- p.Ile424=
- Coding
- c.1272A>T
- MANE Select
- NM_000026
- dbSNP
- rs1057522571
- Type
- single nucleotide variant
- Location
- chr22:40364960 (GRCh38)
- Gene constraint
- LOEUF 0.915 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.82 · 4 PDB
- Residue 424
- an α-helix
Similar variants
- ADSL c.1191+5G>C Pathogenic/Likely pathogenic ★★ same type
- ADSL c.402+1G>T Likely pathogenic ★★ same type
- ADSL c.482+1G>C Likely pathogenic ★★ same type
- ADSL c.-49T>C Pathogenic/Likely pathogenic ★★ same type
- ADSL p.Arg141Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- ADSL p.Arg149Ter Pathogenic/Likely pathogenic ★★ same type
- ADSL p.Arg190Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- ADSL p.Arg190Ter 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/adsl-p-ile424 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown