ADSL c.357+238A>G
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 8.34%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type. | ||
| Splicing | ||
| Splice region | donor +238 | deep intronic (+238 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Non-coding constraint | Z 0.50 | 1 kb window · o/e 0.96 · regional · uncalibrated |
| Overall | ||
| CADD | 0.119 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.34%
African / African-American · 4,240/50,810 alleles
Filtering AF
8.14%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.05%
Overall
0.97%
4,677/482,182 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 8.34% | 12 |
| Admixed American | 0.711% | 141 |
| Remaining individualsnot grpmax-eligible | 0.697% | 143 |
| Middle Eastern | 0.361% | 277 |
| South Asian | 0.0377% | 2,652 |
| European (non-Finnish) | 0.0279% | 3,582 |
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
- Coding
- c.357+238A>G
- MANE Select
- NM_000026
- dbSNP
- rs143135693
- Type
- single nucleotide variant
- Location
- chr22:40350273 (GRCh38)
- Gene constraint
- LOEUF 0.915 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.82 · 4 PDB
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-c-357-plus-238a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown