ASL c.348+8A>T
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.013%, nfe)
Conditions
1
argininosuccinic aciduria
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +8 | near-intronic (+8 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -0.71 |
| Non-coding constraint | Z 2.05 | 1 kb window · o/e 0.86 · regional · uncalibrated |
| Overall | ||
| CADD | 0.421 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.013%
European (non-Finnish) · 153/1,179,940 alleles
Filtering AF
0.0113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0107%
Overall
0.00948%
153/1,613,438 alleles · ultra-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
- ASL
- Coding
- c.348+8A>T
- MANE Select
- NM_000048
- dbSNP
- rs757626168
- Type
- single nucleotide variant
- Location
- chr7:66082944 (GRCh38)
- Gene constraint
- LOEUF 0.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.51 · 2 PDB
Disease context
argininosuccinic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Argininosuccinic aciduria (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
- Prevalence
- 1-9 / 1 000 000 (United States)
Similar variants
- ASL c.1062+5G>C Likely pathogenic ★★ same condition
- ASL c.1143+1G>T Pathogenic/Likely pathogenic ★★ same condition
- ASL c.13-1G>C Pathogenic/Likely pathogenic ★★ same condition
- ASL c.291+1G>T Likely pathogenic ★★ same condition
- ASL c.348+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ASL c.349-1G>A Likely pathogenic ★★ same condition
- ASL c.446+1G>A Pathogenic ★★ same condition
- ASL c.446+2T>C 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/asl-c-348-plus-8a-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown