Is CPS1 p.Cys225Ser (c.674G>C) pathogenic?

CPS1 p.Cys225Ser (c.674G>C) is classified Uncertain significance in CPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-31). AlphaMissense: likely pathogenic (0.7008); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CPS1 p.Cys225Ser (c.674G>C)?

CPS1 p.Cys225Ser (c.674G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CPS1 p.Cys225Ser (c.674G>C) in the general population?

CPS1 p.Cys225Ser (c.674G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPS1 p.Cys225Ser (c.674G>C)?

AlphaMissense predicts likely pathogenic (score 0.7008) — an in-silico prediction, not a clinical call.

CPS1 p.Cys225Ser

c.674G>C · rs2469112667 · VCV2230534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7008 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7008	likely pathogenic
REVEL	0.893	moderately pathogenic-leaning
SaProt	LLR -9.80	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 121 kb · p 0.0019 · regional, not allelic
Overall
CADD	27.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPS1
Protein: p.Cys225Ser
Coding: c.674G>C
MANE Select: NM_001875
dbSNP: rs2469112667
Type: single nucleotide variant
Location: chr2:210588110 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 14 PDB
Residue 225: the glutamine amidotransferase type-1 domain; a β-strand

Full CPS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPS1 p.Cys225= Likely benign ★ same residue
CPS1 p.Ala1400Thr Uncertain significance ★★ ⚠ same condition
CPS1 p.Arg1004Cys Uncertain significance ★★ ⚠ same condition
CPS1 p.Arg238Gln Uncertain significance ★★ ⚠ same condition
CPS1 p.Arg419Trp Uncertain significance ★★ ⚠ same condition
CPS1 p.Arg689His Uncertain significance ★★ ⚠ same condition
CPS1 p.Arg882Cys Uncertain significance ★★ ⚠ same condition
CPS1 p.Asn558Ser Uncertain significance ★★ ⚠ 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-cys225ser (accessed [today's date]).

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