Is CP p.Pro87Leu (c.260C>T) pathogenic?

CP p.Pro87Leu (c.260C>T) is classified Uncertain significance in CP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-12). AlphaMissense: ambiguous (0.382); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with CP p.Pro87Leu (c.260C>T)?

CP p.Pro87Leu (c.260C>T) is associated with Inborn genetic diseases, aceruloplasminemia (ClinVar).

How common is CP p.Pro87Leu (c.260C>T) in the general population?

CP p.Pro87Leu (c.260C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CP p.Pro87Leu (c.260C>T)?

AlphaMissense predicts ambiguous (score 0.382) — an in-silico prediction, not a clinical call.

CP p.Pro87Leu

c.260C>T · rs200823208 · VCV1470883

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.382 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.382	ambiguous
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -10.24	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.61 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.56 · regional, not allelic
Overall
CADD	24.1	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 0.005% Admixed American · 3/60,018 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00167% 27/1,613,930 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,006
Finnishnot grpmax-eligible	0.00313%	31,999
African / African-American	0.00267%	37,503
East Asian	0.00223%	44,846
European (non-Finnish)	0.00161%	62,102

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.Pro87Leu
Coding: c.260C>T
MANE Select: NM_000096
dbSNP: rs200823208
Type: single nucleotide variant
Location: chr3:149212585 (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 87: the plastocyanin-like 1 domain; an α-helix

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

Also linked: aceruloplasminemia

Similar variants

CP p.Pro87Ser Uncertain significance ★★ ⚠ same residue
CP p.Pro87= Likely benign ★ 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

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-pro87leu (accessed [today's date]).

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