Is ASL p.Val403fs (c.1207del) pathogenic?

ASL p.Val403fs (c.1207del) is classified Pathogenic/Likely pathogenic in ASL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-02). Very rare (popmax 0.000254%, nfe); Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Val403fs (c.1207del)?

ASL p.Val403fs (c.1207del) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Val403fs (c.1207del) in the general population?

ASL p.Val403fs (c.1207del) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is Argininosuccinic aciduria inherited?

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

ASL p.Val403fs

c.1207del · rs1554328363 · VCV552410

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (16 of 17, 47 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 3.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,000 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,044 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: ASL
Protein: p.Val403fs
Coding: c.1207del
MANE Select: NM_000048
dbSNP: rs1554328363
Type: Deletion
Location: chr7:66092616 (GRCh38)
Gene constraint: LOEUF 0.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.51 · 2 PDB

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 p.Val403Phe Uncertain significance ★ ⚠ same residue
ASL p.Val403= Likely benign ★ same residue
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

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-val403fs (accessed [today's date]).

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