Is CP p.Trp877Ter (c.2630G>A) pathogenic?

CP p.Trp877Ter (c.2630G>A) is classified Pathogenic in CP (ClinVar, Single submitter, 3 submitters; last evaluated 2025-12-06). Absent from gnomAD v4.1; Associated with aceruloplasminemia.

What condition is associated with CP p.Trp877Ter (c.2630G>A)?

CP p.Trp877Ter (c.2630G>A) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Trp877Ter (c.2630G>A) in the general population?

CP p.Trp877Ter (c.2630G>A) is absent from gnomAD v4.1 (gnomAD).

How is Aceruloplasminemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CP p.Trp877Ter

c.2630G>A · rs121909579 · VCV17562

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

aceruloplasminemia

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 15 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.30	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 2.2, phastCons 1
Overall
CADD	39.0	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

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: CP
Protein: p.Trp877Ter
Coding: c.2630G>A
MANE Select: NM_000096
dbSNP: rs121909579
Type: single nucleotide variant
Location: chr3:149179587 (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 877: 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

aceruloplasminemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Aceruloplasminemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Elderly
Prevalence: 1-9 / 1 000 000 (Japan)

Similar variants

CP p.Trp877Arg Uncertain significance ★★ ⚠ same residue
CP c.1208+1G>A Pathogenic ★★ same condition
CP c.2879-1G>T Likely pathogenic ★★ same condition
CP p.Arg901Ter Pathogenic ★★ same condition
CP p.Gly195Arg Likely pathogenic ★★ same condition
CP p.Gly650Arg Pathogenic/Likely pathogenic ★★ same condition
CP p.Gly708Ser Pathogenic ★★ same condition
CP p.Leu919Pro 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/cp-p-trp877ter (accessed [today's date]).

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