Is CP p.Ser474= (c.1422T>C) pathogenic?

CP p.Ser474= (c.1422T>C) is classified Likely benign in CP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-20). Ultra-rare (popmax 0.0557%, eas); Associated with aceruloplasminemia.

What condition is associated with CP p.Ser474= (c.1422T>C)?

CP p.Ser474= (c.1422T>C) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Ser474= (c.1422T>C) in the general population?

CP p.Ser474= (c.1422T>C) is ultra-rare (popmax 0.0557%, eas) (gnomAD).

How is Aceruloplasminemia inherited?

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

CP p.Ser474=

c.1422T>C · rs570042183 · VCV716747

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0557%, eas)

Conditions

aceruloplasminemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.21	GERP -3.5, phastCons 0.47
Overall
CADD	6.927	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0557% East Asian · 25/44,884 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00211% 34/1,614,148 alleles · ultra-rare exomes 29/1,461,842 · genomes 5/152,306 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0557%	1,795
Remaining individualsnot grpmax-eligible	0.0144%	6,945

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.Ser474=
Coding: c.1422T>C
MANE Select: NM_000096
dbSNP: rs570042183
Type: single nucleotide variant
Location: chr3:149199791 (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 474: the plastocyanin-like 3 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.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-ser474 (accessed [today's date]).

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