Is CPS1 p.Arg882Cys (c.2644C>T) pathogenic?

CPS1 p.Arg882Cys (c.2644C>T) is classified Uncertain significance in CPS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-13). AlphaMissense: likely benign (0.157); Very rare (popmax 0.00401%, afr); Associated with Inborn genetic diseases.

What condition is associated with CPS1 p.Arg882Cys (c.2644C>T)?

CPS1 p.Arg882Cys (c.2644C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CPS1 p.Arg882Cys (c.2644C>T) in the general population?

CPS1 p.Arg882Cys (c.2644C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about CPS1 p.Arg882Cys (c.2644C>T)?

AlphaMissense predicts likely benign (score 0.157) — an in-silico prediction, not a clinical call.

CPS1 p.Arg882Cys

c.2644C>T · rs148519116 · VCV499664

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.157 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.157	likely benign
REVEL	0.791	moderately pathogenic-leaning
SaProt	LLR -9.92	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.94, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 121 kb · p 0.0019 · regional, not allelic
Overall
CADD	31.0	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 0.00401% African / African-American · 3/74,760 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000496% 8/1,611,446 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,920
South Asian	0.0022%	45,520
European (non-Finnish)	0.000255%	392,713

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.Arg882Cys
Coding: c.2644C>T
MANE Select: NM_001875
dbSNP: rs148519116
Type: single nucleotide variant
Location: chr2:210616498 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 14 PDB
Residue 882: an α-helix

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.Arg882His 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.Asn558Ser Uncertain significance ★★ ⚠ same condition
CPS1 p.Glu1221Gly 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-arg882cys (accessed [today's date]).

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