Is CPS1 p.Phe73fs (c.209_216dup) pathogenic?

CPS1 p.Phe73fs (c.209216dup) is classified Likely pathogenic in CPS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-06-21). Absent from gnomAD; Associated with carbamoyl phosphate synthetase I deficiency disease.

What condition is associated with CPS1 p.Phe73fs (c.209_216dup)?

CPS1 p.Phe73fs (c.209_216dup) is associated with carbamoyl phosphate synthetase I deficiency disease, pulmonary hypertension, neonatal, susceptibility to (ClinVar).

How common is CPS1 p.Phe73fs (c.209_216dup) in the general population?

CPS1 p.Phe73fs (c.209_216dup) 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.Phe73fs

c.209_216dup · rs1553509010 · VCV417895

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

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 2 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.7, 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: CPS1
Protein: p.Phe73fs
Coding: c.209_216dup
MANE Select: NM_001875
dbSNP: rs1553509010
Type: Duplication
Location: chr2:210573379 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 14 PDB
Residue 73: a β-strand; the 'anthranilate phosphoribosyltransferase homolog' region

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

Also linked: pulmonary hypertension, neonatal, susceptibility to

For Carbamoyl-phosphate synthetase 1 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPS1 p.Asn103_Gly104dup Pathogenic/Likely pathogenic ★★ same condition
CPS1 p.Asp442Ter Pathogenic/Likely pathogenic ★★ same condition
CPS1 p.Gly802fs Pathogenic/Likely pathogenic ★★ same condition
CPS1 p.Leu290fs Pathogenic/Likely pathogenic ★★ same condition
CPS1 c.3666+77dup Benign ★★ same condition
CPS1 c.3928-8dup Likely benign ★★ same condition
CPS1 p.Ala1102fs Pathogenic ★ same condition
CPS1 p.Asn472fs 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-phe73fs (accessed [today's date]).

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