Is CP p.Glu577fs (c.1731del) pathogenic?

CP p.Glu577fs (c.1731del) is classified Pathogenic in CP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-16). Very rare (popmax 0.000254%, nfe); Associated with aceruloplasminemia.

What condition is associated with CP p.Glu577fs (c.1731del)?

CP p.Glu577fs (c.1731del) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Glu577fs (c.1731del) in the general population?

CP p.Glu577fs (c.1731del) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is Aceruloplasminemia inherited?

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

CP p.Glu577fs

c.1731del · rs2108244261 · VCV1451712

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

aceruloplasminemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,392 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000206% 3/1,459,598 alleles · very rare

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.Glu577fs
Coding: c.1731del
MANE Select: NM_000096
dbSNP: rs2108244261
Type: Deletion
Location: chr3:149188185 (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 577: a β-strand; the plastocyanin-like 4 domain

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 c.607+1del Pathogenic/Likely pathogenic ★★ same condition
CP p.Pro689fs Pathogenic/Likely pathogenic ★★ same condition
CP p.Met1* Uncertain significance ★★ same condition
CP c.2286-15_2286-14del Benign/Likely benign ★★ same condition
CP c.2286-15del Benign ★★ same condition
CP c.2286-4del Benign/Likely benign ★★ same condition
CP c.2078-75_2241del Likely pathogenic ★ same condition
CP p.Ala675fs 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-glu577fs (accessed [today's date]).

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