Is ASS1 p.Arg108= (c.322C>A) pathogenic?

ASS1 p.Arg108= (c.322C>A) is classified Likely benign in ASS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-06). Very rare (popmax 0.00659%, sas); Associated with citrullinemia.

What condition is associated with ASS1 p.Arg108= (c.322C>A)?

ASS1 p.Arg108= (c.322C>A) is associated with citrullinemia (ClinVar).

How common is ASS1 p.Arg108= (c.322C>A) in the general population?

ASS1 p.Arg108= (c.322C>A) is very rare (popmax 0.00659%, sas) (gnomAD).

ASS1 p.Arg108=

c.322C>A · rs143405567 · VCV1548255

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

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 0.034	GERP -1.1, phastCons 0.86
Overall
CADD	9.649	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,042 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000434% 7/1,613,172 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,174
European (non-Finnish)	8.48e-05%	1,179,883

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.Arg108=
Coding: c.322C>A
MANE Select: NM_054012
dbSNP: rs143405567
Type: single nucleotide variant
Location: chr9:130458548 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 108: 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 p.Arg108Gln Uncertain significance ★ ⚠ same residue
ASS1 p.Arg108Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ASS1 p.Arg108Trp 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

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-arg108 (accessed [today's date]).

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