Is ASS1 p.Lys53= (c.159G>A) pathogenic?

ASS1 p.Lys53= (c.159G>A) is classified Likely benign in ASS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-29). Absent from gnomAD v4.1; Associated with citrullinemia.

What condition is associated with ASS1 p.Lys53= (c.159G>A)?

ASS1 p.Lys53= (c.159G>A) is associated with citrullinemia (ClinVar).

How common is ASS1 p.Lys53= (c.159G>A) in the general population?

ASS1 p.Lys53= (c.159G>A) is absent from gnomAD v4.1 (gnomAD).

ASS1 p.Lys53=

c.159G>A · rs2131869324 · VCV1097937

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

citrullinemia

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 3.8	GERP -2.1, phastCons 1
Overall
CADD	9.621	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASS1
Protein: p.Lys53=
Coding: c.159G>A
MANE Select: NM_054012
dbSNP: rs2131869324
Type: single nucleotide variant
Location: chr9:130454358 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 53: an α-helix; a UniProt-annotated variant site (in ctln1)

Full ASS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

citrullinemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASS1 c.1194-1G>C Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.174+1G>A Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.174+1G>T Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.175-1119G>A Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.364-2A>T Likely pathogenic ★★ same condition
ASS1 c.421-2A>G Pathogenic ★★ same condition
ASS1 c.496-2A>G Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.689-2A>C 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/ass1-p-lys53 (accessed [today's date]).

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