Is ASS1 p.Arg95fs (c.285del) pathogenic?

ASS1 p.Arg95fs (c.285del) is classified Likely pathogenic in ASS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-01). Very rare (popmax 0.00267%, afr); Associated with citrullinemia type I.

What condition is associated with ASS1 p.Arg95fs (c.285del)?

ASS1 p.Arg95fs (c.285del) is associated with citrullinemia type I (ClinVar).

How common is ASS1 p.Arg95fs (c.285del) in the general population?

ASS1 p.Arg95fs (c.285del) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Citrullinemia type I inherited?

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

ASS1 p.Arg95fs

c.285del · rs1333271656 · VCV2679022

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

citrullinemia type I

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP -0.58, phastCons 1
Overall
CADD	34.0	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 0.00267% African / African-American · 2/74,888 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00131% 2/152,186 alleles · very rare

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.Arg95fs
Coding: c.285del
MANE Select: NM_054012
dbSNP: rs1333271656
Type: Deletion
Location: chr9:130458510 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 95: an α-helix; a UniProt-annotated variant site (in ctln1); a UniProt-annotated variant site (in ctln1; increased thermal stability; loss of argininosuccinate synthase activity)

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

Disease context

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

For Citrullinemia type I (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ASS1 p.Gln107fs Pathogenic/Likely pathogenic ★★ same condition
ASS1 p.Gln350fs Likely pathogenic ★★ same condition
ASS1 p.Glu283fs Pathogenic ★★ same condition
ASS1 p.Glu298fs Pathogenic ★★ same condition
ASS1 p.Phe150fs Pathogenic/Likely pathogenic ★★ same condition
ASS1 p.Phe154fs Pathogenic/Likely pathogenic ★★ same condition
ASS1 p.Phe317fs Pathogenic ★★ same condition
ASS1 p.Ser131fs 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-arg95fs (accessed [today's date]).

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