Is ASS1 p.Phe44fs (c.130_132delinsA) pathogenic?

ASS1 p.Phe44fs (c.130132delinsA) is classified Likely pathogenic in ASS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-16). Absent from gnomAD; Associated with citrullinemia type I.

What condition is associated with ASS1 p.Phe44fs (c.130_132delinsA)?

ASS1 p.Phe44fs (c.130_132delinsA) is associated with citrullinemia type I (ClinVar).

How common is ASS1 p.Phe44fs (c.130_132delinsA) in the general population?

ASS1 p.Phe44fs (c.130_132delinsA) is absent from gnomAD (gnomAD).

How is Citrullinemia type I inherited?

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

ASS1 p.Phe44fs

c.130_132delinsA · rs2490520604 · VCV1726350

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ASS1
Protein: p.Phe44fs
Coding: c.130_132delinsA
MANE Select: NM_054012
dbSNP: rs2490520604
Type: Indel
Location: chr9:130454329 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 44: 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 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.Cys331fs Likely pathogenic ★ same condition
ASS1 p.Tyr207fs Likely pathogenic ★ same condition
ASS1 p.Phe44Leu Uncertain significance ★ ⚠ same residue
ASS1 p.Phe44= Likely benign ★ same residue
ASS1 c.1128-6_1188dup Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.1194-19_1197dup Likely pathogenic ★★ same condition
ASS1 c.1194-1G>C Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.174+1G>A 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-phe44fs (accessed [today's date]).

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