Is ADSL p.Arg396fs (c.1187del) pathogenic?

ADSL p.Arg396fs (c.1187del) is classified Pathogenic in ADSL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). Absent from gnomAD; Associated with adenylosuccinate lyase deficiency.

What condition is associated with ADSL p.Arg396fs (c.1187del)?

ADSL p.Arg396fs (c.1187del) is associated with adenylosuccinate lyase deficiency (ClinVar).

How common is ADSL p.Arg396fs (c.1187del) in the general population?

ADSL p.Arg396fs (c.1187del) is absent from gnomAD (gnomAD).

How is Adenylosuccinate lyase deficiency inherited?

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

ADSL p.Arg396fs

c.1187del · rs2044916556 · VCV935347

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

adenylosuccinate lyase deficiency

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 11 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 1.4, 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: ADSL
Protein: p.Arg396fs
Coding: c.1187del
MANE Select: NM_000026
dbSNP: rs2044916556
Type: Deletion
Location: chr22:40364361 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.82 · 4 PDB
Residue 396: a UniProt-annotated variant site (in adsld; severe; abolishes cooperativity and reduces enzyme activity); an α-helix

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

Disease context

adenylosuccinate lyase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Adenylosuccinate lyase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ADSL p.Arg396Cys Pathogenic/Likely pathogenic ★★ same residue
ADSL p.Arg396His Pathogenic/Likely pathogenic ★★ same residue
ADSL p.Asn421del Uncertain significance ★★ same condition
ADSL c.1368+8del Likely benign ★★ same condition
ADSL p.Arg125fs Pathogenic ★ same condition
ADSL p.Asp223fs Pathogenic ★ same condition
ADSL p.Gln63fs Pathogenic ★ same condition
ADSL p.Glu343fs 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/adsl-p-arg396fs (accessed [today's date]).

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