Is ADSL p.Ala90= (c.270T>C) pathogenic?

ADSL p.Ala90= (c.270T>C) is classified Conflicting classifications of pathogenicity in ADSL (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-13). Rare (popmax 0.129%, afr); Associated with adenylosuccinate lyase deficiency.

What condition is associated with ADSL p.Ala90= (c.270T>C)?

ADSL p.Ala90= (c.270T>C) is associated with adenylosuccinate lyase deficiency (ClinVar).

How common is ADSL p.Ala90= (c.270T>C) in the general population?

ADSL p.Ala90= (c.270T>C) is rare (popmax 0.129%, afr) (gnomAD).

How is Adenylosuccinate lyase deficiency inherited?

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

ADSL p.Ala90=

c.270T>C · rs143275316 · VCV254723

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.129%, 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
Constraint at this position
Conservation	phyloP -0.2	GERP -0.011, phastCons 0.65
Overall
CADD	10.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.129% African / African-American · 97/74,908 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.00675% 109/1,614,028 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.129%	772
Remaining individualsnot grpmax-eligible	0.0176%	5,680
Admixed American	0.00167%	59,990

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.Ala90=
Coding: c.270T>C
MANE Select: NM_000026
dbSNP: rs143275316
Type: single nucleotide variant
Location: chr22:40349948 (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 90: 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.Ala90Thr Pathogenic ★ same residue
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

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-ala90 (accessed [today's date]).

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