Is ADSL c.482+8A>G pathogenic?

ADSL c.482+8A>G is classified Uncertain significance in ADSL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2016-08-24). Very rare (popmax 0.00892%, eas); Associated with adenylosuccinate lyase deficiency.

What condition is associated with ADSL c.482+8A>G?

ADSL c.482+8A>G is associated with adenylosuccinate lyase deficiency (ClinVar).

How common is ADSL c.482+8A>G in the general population?

ADSL c.482+8A>G is very rare (popmax 0.00892%, eas) (gnomAD).

How is Adenylosuccinate lyase deficiency inherited?

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

ADSL c.482+8A>G

rs886042606 · VCV283351

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

adenylosuccinate lyase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +8	near-intronic (+8 nt from the splice site)
SpliceAI	Δ0.90	donor gain · deltas
Pangolin	Δ0.75	gain · loss 0.26 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.1	GERP -3, phastCons 0.016
Overall
CADD	7.551	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,866 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000274% 4/1,457,444 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: ADSL
Coding: c.482+8A>G
MANE Select: NM_000026
dbSNP: rs886042606
Type: single nucleotide variant
Location: chr22:40354335 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.82 · 4 PDB

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 c.1191+5G>C Pathogenic/Likely pathogenic ★★ same condition
ADSL c.402+1G>T Likely pathogenic ★★ same condition
ADSL c.482+1G>C Likely pathogenic ★★ same condition
ADSL c.-49T>C Pathogenic/Likely pathogenic ★★ same condition
ADSL p.Arg141Trp Pathogenic/Likely pathogenic ★★ same condition
ADSL p.Arg149Ter Pathogenic/Likely pathogenic ★★ same condition
ADSL p.Arg190Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ADSL p.Arg190Ter 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-c-482-plus-8a-g (accessed [today's date]).

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