Is ASL p.Pro19fs (c.56_57del) pathogenic?

ASL p.Pro19fs (c.5657del) is classified Likely pathogenic in ASL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-29). Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Pro19fs (c.56_57del)?

ASL p.Pro19fs (c.56_57del) is associated with argininosuccinic aciduria (ClinVar).

How is Argininosuccinic aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ASL p.Pro19fs

c.56_57del · VCV4818329

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

argininosuccinic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ASL
Protein: p.Pro19fs
Coding: c.56_57del
MANE Select: NM_000048
Type: Deletion
Location: chr7:66081844 (GRCh38)
Gene constraint: LOEUF 0.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.51 · 2 PDB
Residue 19: an α-helix

Full ASL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

argininosuccinic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Argininosuccinic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

ASL c.1045_1062+7del Pathogenic ★★ same condition
ASL c.1143+1del Likely pathogenic ★★ same condition
ASL p.Asp38fs Pathogenic/Likely pathogenic ★★ same condition
ASL p.Leu325fs Pathogenic ★★ same condition
ASL p.Leu419fs Pathogenic/Likely pathogenic ★★ same condition
ASL p.Val211fs Pathogenic ★★ same condition
ASL p.Val349fs Pathogenic ★★ same condition
ASL p.Val403fs Pathogenic/Likely 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-p-pro19fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown