Is ASS1 p.Arg157= (c.471C>T) pathogenic?

ASS1 p.Arg157= (c.471C>T) is classified Likely benign in ASS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-12). Very rare (popmax 0.0011%, sas); Associated with citrullinemia.

What condition is associated with ASS1 p.Arg157= (c.471C>T)?

ASS1 p.Arg157= (c.471C>T) is associated with citrullinemia (ClinVar).

How common is ASS1 p.Arg157= (c.471C>T) in the general population?

ASS1 p.Arg157= (c.471C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

ASS1 p.Arg157=

c.471C>T · rs746022332 · VCV2712554

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

citrullinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.29	GERP 0.35, phastCons 0.95
Overall
CADD	9.587	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,092 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,036 alleles · very rare exomes 2/1,461,796 · genomes 1/152,240 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,092
European (non-Finnish)	0.000169%	590,016

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: ASS1
Protein: p.Arg157=
Coding: c.471C>T
MANE Select: NM_054012
dbSNP: rs746022332
Type: single nucleotide variant
Location: chr9:130466775 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 157: a UniProt-annotated variant site (in ctln1); a UniProt-annotated variant site (in ctln1; decreased thermal stability; loss of argininosuccinate synthase activity); a UniProt-annotated variant site (in ctln1; loss of argininosuccinate synthase activity)

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 p.Arg157Cys Pathogenic ★★ same residue
ASS1 p.Arg157His Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-arg157 (accessed [today's date]).

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