Is CP p.Tyr857= (c.2571C>T) pathogenic?

CP p.Tyr857= (c.2571C>T) is classified Conflicting classifications of pathogenicity in CP (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-05-01). Rare (popmax 0.363%, nfe); Associated with aceruloplasminemia.

What condition is associated with CP p.Tyr857= (c.2571C>T)?

CP p.Tyr857= (c.2571C>T) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Tyr857= (c.2571C>T) in the general population?

CP p.Tyr857= (c.2571C>T) is rare (popmax 0.363%, nfe) (gnomAD).

How is Aceruloplasminemia inherited?

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

CP p.Tyr857=

c.2571C>T · rs151304828 · VCV210756

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.363%, nfe)

Conditions

aceruloplasminemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.94 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.3	GERP -0.51
Overall
CADD	5.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.363% European (non-Finnish) · 4,260/1,173,450 alleles

Filtering AF 0.354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.35%

Overall 0.288% 4,625/1,603,502 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.363%	275
Remaining individualsnot grpmax-eligible	0.281%	356
Admixed American	0.131%	765
African / African-American	0.0725%	1,380
Ashkenazi Jewishnot grpmax-eligible	0.0582%	1,720
Finnishnot grpmax-eligible	0.0446%	2,244
Middle Eastern	0.0166%	6,012
South Asian	0.0099%	10,104
East Asian	0.00908%	11,017

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.Tyr857=
Coding: c.2571C>T
MANE Select: NM_000096
dbSNP: rs151304828
Type: single nucleotide variant
Location: chr3:149179646 (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 857: a β-strand; the plastocyanin-like 5 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 p.Tyr857His Uncertain significance ★ ⚠ same residue
HPS3 p.Glu857= 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-tyr857 (accessed [today's date]).

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