Is CP p.Val223= (c.669G>C) pathogenic?

CP p.Val223= (c.669G>C) is classified Benign in CP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Low-frequency (popmax 2.05%, afr); Associated with aceruloplasminemia.

What condition is associated with CP p.Val223= (c.669G>C)?

CP p.Val223= (c.669G>C) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Val223= (c.669G>C) in the general population?

CP p.Val223= (c.669G>C) is low-frequency (popmax 2.05%, afr) (gnomAD).

How is Aceruloplasminemia inherited?

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

CP p.Val223=

c.669G>C · rs35438054 · VCV343785

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.05%, afr)

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 · C>T here scores Δ0.90 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5	GERP 0.42, phastCons 1
Overall
CADD	13.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.05% African / African-American · 1,534/75,006 alleles

Filtering AF 1.96% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.93%

Overall 0.11% 1,771/1,613,756 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.05%	49
Admixed American	0.155%	645
Remaining individualsnot grpmax-eligible	0.107%	933
Middle Eastern	0.0165%	6,058
European (non-Finnish)	0.00636%	15,730
South Asian	0.0011%	91,062

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.Val223=
Coding: c.669G>C
MANE Select: NM_000096
dbSNP: rs35438054
Type: single nucleotide variant
Location: chr3:149209323 (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 223: the plastocyanin-like 2 domain; a β-strand

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.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
CP p.Val219Glu 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-val223 (accessed [today's date]).

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