Is CPS1 p.Val409fs (c.1221_1222del) pathogenic?

CPS1 p.Val409fs (c.12211222del) is classified Pathogenic in CPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-23). Absent from gnomAD; Associated with carbamoyl phosphate synthetase I deficiency disease.

What condition is associated with CPS1 p.Val409fs (c.1221_1222del)?

CPS1 p.Val409fs (c.1221_1222del) is associated with carbamoyl phosphate synthetase I deficiency disease (ClinVar).

How common is CPS1 p.Val409fs (c.1221_1222del) in the general population?

CPS1 p.Val409fs (c.1221_1222del) is absent from gnomAD (gnomAD).

How is Carbamoyl-phosphate synthetase 1 deficiency inherited?

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

CPS1 p.Val409fs

c.1221_1222del · rs1574566640 · VCV1940644

Pathogenic Single submitter

Classification

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

carbamoyl phosphate synthetase I deficiency disease

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 12 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 2.9, 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: CPS1
Protein: p.Val409fs
Coding: c.1221_1222del
MANE Select: NM_001875
dbSNP: rs1574566640
Type: Deletion
Location: chr2:210594564 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 14 PDB

Full CPS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

carbamoyl phosphate synthetase I deficiency disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Carbamoyl-phosphate synthetase 1 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPS1 p.Val409= Likely benign ★ same residue
CPS1 p.Val409Ala Likely benign ★ ⚠ same residue
CPS1 p.Ala907fs Pathogenic/Likely pathogenic ★★ same condition
CPS1 p.Arg1228fs Pathogenic/Likely pathogenic ★★ same condition
CPS1 p.Arg932_Leu933insTer Pathogenic ★★ same condition
CPS1 p.Asp1304fs Pathogenic ★★ same condition
CPS1 p.Asp642fs Pathogenic/Likely pathogenic ★★ same condition
CPS1 p.Cys644fs 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/cps1-p-val409fs (accessed [today's date]).

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