ADSL c.357+112del
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 26.2%, sas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +112 | deep intronic (+112 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -3 | GERP -2.6 |
| Non-coding constraint | Z 0.50 | 1 kb window · o/e 0.96 · regional · uncalibrated |
| Overall | ||
| CADD | 4.21 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
26.2%
South Asian · 12,382/47,310 alleles
Filtering AF
25.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 25.6%
Overall
19.9%
157,137/787,938 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 26.2% | 4 |
| East Asian | 24.5% | 4 |
| Remaining individualsnot grpmax-eligible | 24% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 22.3% | 4 |
| Middle Eastern | 21.6% | 5 |
| European (non-Finnish) | 20.5% | 5 |
| Finnishnot grpmax-eligible | 20.1% | 5 |
| Admixed American | 16% | 6 |
| African / African-American | 6.25% | 16 |
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+112del
- MANE Select
- NM_000026
- dbSNP
- rs373063501
- Type
- Deletion
- Location
- chr22:40350134 (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 p.Asn421del Uncertain significance ★★ same type
- ADSL c.1368+8del Likely benign ★★ same type
- ADSL c.483-41_483-38del Benign ★★ same type
- ADSL p.Arg125fs Pathogenic ★ same type
- ADSL p.Arg396fs Pathogenic ★ same type
- ADSL p.Asp223fs Pathogenic ★ same type
- ADSL p.Gln63fs Pathogenic ★ same type
- ADSL p.Glu343fs 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-112del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown