Is ADSL p.Ser9= (c.27G>T) pathogenic?

ADSL p.Ser9= (c.27G>T) is classified Benign/Likely benign in ADSL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-19). Rare (popmax 0.149%, afr); Associated with adenylosuccinate lyase deficiency.

What condition is associated with ADSL p.Ser9= (c.27G>T)?

ADSL p.Ser9= (c.27G>T) is associated with adenylosuccinate lyase deficiency (ClinVar).

How common is ADSL p.Ser9= (c.27G>T) in the general population?

ADSL p.Ser9= (c.27G>T) is rare (popmax 0.149%, afr) (gnomAD).

How is Adenylosuccinate lyase deficiency inherited?

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

ADSL p.Ser9=

c.27G>T · rs146873132 · VCV136310

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.149%, afr)

Conditions

adenylosuccinate lyase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.26	GERP -3.1
Overall
CADD	5.268	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.149% African / African-American · 112/74,968 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.118%

Overall 0.0076% 122/1,605,858 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.149%	669
Middle Eastern	0.0165%	6,052
Remaining individualsnot grpmax-eligible	0.0113%	8,871
South Asian	0.00112%	89,596
European (non-Finnish)	8.5e-05%	1,177,094

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
Protein: p.Ser9=
Coding: c.27G>T
MANE Select: NM_000026
dbSNP: rs146873132
Type: single nucleotide variant
Location: chr22:40346585 (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-p-ser9 (accessed [today's date]).

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