Is CPS1 p.Gln44Ter (c.130C>T) pathogenic?

CPS1 p.Gln44Ter (c.130C>T) is classified Pathogenic in CPS1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-02). Very rare (popmax 0.00223%, eas); Associated with pulmonary hypertension, neonatal, susceptibility to.

What condition is associated with CPS1 p.Gln44Ter (c.130C>T)?

CPS1 p.Gln44Ter (c.130C>T) is associated with pulmonary hypertension, neonatal, susceptibility to, carbamoyl phosphate synthetase I deficiency disease (ClinVar).

How common is CPS1 p.Gln44Ter (c.130C>T) in the general population?

CPS1 p.Gln44Ter (c.130C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CPS1 p.Gln44Ter

c.130C>T · rs121912593 · VCV2420

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

pulmonary hypertension, neonatal, susceptibility to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 38
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.65 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,874 alleles

Overall 6.85e-05% 1/1,460,268 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.Gln44Ter
Coding: c.130C>T
MANE Select: NM_001875
dbSNP: rs121912593
Type: single nucleotide variant
Location: chr2:210573301 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 14 PDB
Residue 44: the 'anthranilate phosphoribosyltransferase homolog' region

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 c.1086+1G>A Likely pathogenic ★★ same condition
CPS1 c.1087-1G>T Pathogenic/Likely pathogenic ★★ same condition
CPS1 c.1165-2A>G Likely pathogenic ★★ same condition
CPS1 c.1263+5G>C Pathogenic/Likely pathogenic ★★ same condition
CPS1 c.1549+1G>A Pathogenic/Likely pathogenic ★★ same condition
CPS1 c.1549+1G>T Pathogenic/Likely pathogenic ★★ same condition
CPS1 c.1837-8A>G Pathogenic/Likely pathogenic ★★ same condition
CPS1 c.1981+1G>C 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-gln44ter (accessed [today's date]).

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