Is CPS1 p.Pro1302fs (c.3903del) pathogenic?

CPS1 p.Pro1302fs (c.3903del) is classified Pathogenic/Likely pathogenic in CPS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-14). Very rare (popmax 0.00161%, nfe); Associated with pulmonary hypertension, neonatal, susceptibility to.

What condition is associated with CPS1 p.Pro1302fs (c.3903del)?

CPS1 p.Pro1302fs (c.3903del) is associated with pulmonary hypertension, neonatal, susceptibility to, carbamoyl phosphate synthetase I deficiency disease (ClinVar).

How common is CPS1 p.Pro1302fs (c.3903del) in the general population?

CPS1 p.Pro1302fs (c.3903del) is very rare (popmax 0.00161%, nfe) (gnomAD).

CPS1 p.Pro1302fs

c.3903del · rs1264586092 · VCV852940

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Conditions

pulmonary hypertension, neonatal, susceptibility to

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 32 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.4	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,179,976 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.0013% 19/1,461,792 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: CPS1
Protein: p.Pro1302fs
Coding: c.3903del
MANE Select: NM_001875
dbSNP: rs1264586092
Type: Deletion
Location: chr2:210660630 (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

pulmonary hypertension, neonatal, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: carbamoyl phosphate synthetase I deficiency disease

Similar variants

CPS1 p.Pro1302= 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
CPS1 p.Glu455fs 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-pro1302fs (accessed [today's date]).

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