Is CP p.Ser501Arg (c.1501A>C) pathogenic?

CP p.Ser501Arg (c.1501A>C) is classified Uncertain significance in CP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-04-15). AlphaMissense: likely benign (0.1052); Rare (popmax 0.144%, afr); Associated with aceruloplasminemia.

What condition is associated with CP p.Ser501Arg (c.1501A>C)?

CP p.Ser501Arg (c.1501A>C) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Ser501Arg (c.1501A>C) in the general population?

CP p.Ser501Arg (c.1501A>C) is rare (popmax 0.144%, afr) (gnomAD).

How is Aceruloplasminemia inherited?

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

What do computational predictors say about CP p.Ser501Arg (c.1501A>C)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

CP p.Ser501Arg

c.1501A>C · rs139756428 · VCV1495889

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.144%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.55	indeterminate
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -4.1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.56 · regional, not allelic
Overall
CADD	8.799	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.144% African / African-American · 108/75,054 alleles

Filtering AF 0.122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.114%

Overall 0.00756% 122/1,614,082 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.144%	695
Remaining individualsnot grpmax-eligible	0.0144%	6,944
Admixed American	0.00333%	30,006
South Asian	0.00329%	30,361

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.Ser501Arg
Coding: c.1501A>C
MANE Select: NM_000096
dbSNP: rs139756428
Type: single nucleotide variant
Location: chr3:149199712 (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 501: 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

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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-ser501arg (accessed [today's date]).

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