Is CPS1 p.Ser673fs (c.2017_2018del) pathogenic?

CPS1 p.Ser673fs (c.20172018del) is classified Likely pathogenic in CPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-27). No gnomAD frequency available for this variant; Associated with carbamoyl phosphate synthetase I deficiency disease.

What condition is associated with CPS1 p.Ser673fs (c.2017_2018del)?

CPS1 p.Ser673fs (c.2017_2018del) is associated with carbamoyl phosphate synthetase I deficiency disease (ClinVar).

How common is CPS1 p.Ser673fs (c.2017_2018del) in the general population?

CPS1 p.Ser673fs (c.2017_2018del) is no gnomAD frequency available for this variant (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.Ser673fs

c.2017_2018del · rs2469168948 · VCV1724792

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

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 18 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.6	GERP -5.8

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.Ser673fs
Coding: c.2017_2018del
MANE Select: NM_001875
dbSNP: rs2469168948
Type: Microsatellite
Location: chr2:210606763 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 14 PDB
Residue 673: the atp-grasp 1 domain

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.Ser673= Likely benign ★ same residue
CPS1 p.Cys648fs Pathogenic/Likely pathogenic ★★ same condition
CPS1 p.Val1013del Pathogenic/Likely pathogenic ★★ same condition
CPS1 c.1263+8TG[4] Likely benign ★★ same condition
CPS1 p.Ala724fs Pathogenic ★ same condition
CPS1 p.Arg1326fs Likely pathogenic ★ same condition
CPS1 p.Cys225fs Likely pathogenic ★ same condition
CPS1 p.Gly524fs 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/cps1-p-ser673fs (accessed [today's date]).

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