Is ADSL p.Arg190Ter (c.568C>T) pathogenic?

ADSL p.Arg190Ter (c.568C>T) is classified Pathogenic in ADSL (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-19). Very rare (popmax 0.005%, amr); Associated with ADSL-related disorder.

What condition is associated with ADSL p.Arg190Ter (c.568C>T)?

ADSL p.Arg190Ter (c.568C>T) is associated with ADSL-related disorder, adenylosuccinate lyase deficiency (ClinVar).

How common is ADSL p.Arg190Ter (c.568C>T) in the general population?

ADSL p.Arg190Ter (c.568C>T) is very rare (popmax 0.005%, amr) (gnomAD).

ADSL p.Arg190Ter

c.568C>T · rs750614500 · VCV204814

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

ADSL-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,008 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00164% 24/1,461,878 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
European (non-Finnish)	0.00178%	56,192

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.Arg190Ter
Coding: c.568C>T
MANE Select: NM_000026
dbSNP: rs750614500
Type: single nucleotide variant
Location: chr22:40358949 (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 190: a UniProt-annotated variant site (in adsld; moderate); an α-helix

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

Disease context

ADSL-related disorder

Also linked: adenylosuccinate lyase deficiency

Similar variants

ADSL p.Arg190Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
ADSL p.Arg190Gly Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg190ter (accessed [today's date]).

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