Is CP p.Cys874Arg (c.2620T>C) pathogenic?

CP p.Cys874Arg (c.2620T>C) is classified Uncertain significance in CP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely pathogenic (0.9483); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CP p.Cys874Arg (c.2620T>C)?

CP p.Cys874Arg (c.2620T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CP p.Cys874Arg (c.2620T>C) in the general population?

CP p.Cys874Arg (c.2620T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CP p.Cys874Arg (c.2620T>C)?

AlphaMissense predicts likely pathogenic (score 0.9483) — an in-silico prediction, not a clinical call.

CP p.Cys874Arg

c.2620T>C · VCV3496163

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9483 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9483	likely pathogenic · top 4% in CP
REVEL	0.967	strongly pathogenic-leaning
SaProt	LLR -15.62	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 2.5e-07 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,696 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
European (non-Finnish)	0.00017%	589,960

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: CP
Protein: p.Cys874Arg
Coding: c.2620T>C
MANE Select: NM_000096
Type: single nucleotide variant
Location: chr3:149179597 (GRCh38)
Gene constraint: LOEUF 0.624 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.79 · 4 PDB
Residue 874: a β-strand; the plastocyanin-like 5 domain; a disulfide bond

Full CP 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

CP p.Cys874Tyr Uncertain significance ★ ⚠ same residue
CP p.Cys874= Likely benign ★ same residue
CP p.Asn397Lys Uncertain significance ★★ ⚠ same condition
CP p.Asp654Asn Uncertain significance ★★ ⚠ same condition
CP p.Glu742Gln Uncertain significance ★★ ⚠ same condition
CP p.Glu754Lys Uncertain significance ★★ ⚠ same condition
CP p.Glu803Gln Uncertain significance ★★ ⚠ same condition
CP p.Gly730Val 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/cp-p-cys874arg (accessed [today's date]).

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