Is CPS1 p.Asn970Ser (c.2909A>G) pathogenic?

CPS1 p.Asn970Ser (c.2909A>G) is classified Conflicting classifications of pathogenicity in CPS1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.0617); Rare (popmax 0.129%, afr); Associated with pulmonary hypertension, neonatal, susceptibility to.

What condition is associated with CPS1 p.Asn970Ser (c.2909A>G)?

CPS1 p.Asn970Ser (c.2909A>G) is associated with pulmonary hypertension, neonatal, susceptibility to, carbamoyl phosphate synthetase I deficiency disease (ClinVar).

How common is CPS1 p.Asn970Ser (c.2909A>G) in the general population?

CPS1 p.Asn970Ser (c.2909A>G) is rare (popmax 0.129%, afr) (gnomAD).

What do computational predictors say about CPS1 p.Asn970Ser (c.2909A>G)?

AlphaMissense predicts likely benign (score 0.0617) — an in-silico prediction, not a clinical call.

CPS1 p.Asn970Ser

c.2909A>G · rs150485422 · VCV567695

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0617 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.129%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pulmonary hypertension, neonatal, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.0617	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -5.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP 1.7
Regional constraint	o/e 0.93	unconstrained · MANE · 121 kb · p 0.0019 · regional, not allelic
Overall
CADD	14.03	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.129% African / African-American · 97/74,954 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.0186% 299/1,611,220 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.129%	773
Remaining individualsnot grpmax-eligible	0.016%	6,241
European (non-Finnish)	0.0158%	6,333
Admixed American	0.005%	20,003
East Asian	0.00447%	22,390
Finnishnot grpmax-eligible	0.00157%	63,610

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.Asn970Ser
Coding: c.2909A>G
MANE Select: NM_001875
dbSNP: rs150485422
Type: single nucleotide variant
Location: chr2:210640009 (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.Asn970Asp Likely benign ★ same residue
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

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-asn970ser (accessed [today's date]).

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