Is ASL p.Arg95fs (c.283_285delinsGGCG) pathogenic?

ASL p.Arg95fs (c.283285delinsGGCG) is classified Pathogenic in ASL (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-07). Absent from gnomAD; Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Arg95fs (c.283_285delinsGGCG)?

ASL p.Arg95fs (c.283_285delinsGGCG) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Arg95fs (c.283_285delinsGGCG) in the general population?

ASL p.Arg95fs (c.283_285delinsGGCG) is absent from gnomAD (gnomAD).

How is Argininosuccinic aciduria inherited?

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

ASL p.Arg95fs

c.283_285delinsGGCG · rs1554326365 · VCV555261

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 4 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 1.6, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ASL
Protein: p.Arg95fs
Coding: c.283_285delinsGGCG
MANE Select: NM_000048
dbSNP: rs1554326365
Type: Indel
Location: chr7:66082443 (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 95: a UniProt-annotated variant site (in arginsa; loss of argininosuccinate lyase activity); a UniProt-annotated variant site (in arginsa); 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 p.Arg95Cys Pathogenic/Likely pathogenic ★★ same residue
ASL p.Arg95His Pathogenic/Likely pathogenic ★★ ⚠ same residue
ASL p.Arg95_Leu96insArg Uncertain significance ★ same residue
ASL p.Arg95= Likely benign ★ same residue
ASL p.Ser391Ter Pathogenic ★ same condition
ASL p.Thr233fs Likely pathogenic ★ same condition
ASL c.1045_1062+7del Pathogenic ★★ same condition
ASL c.1062+5G>C 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-arg95fs (accessed [today's date]).

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