Is CP p.Arg215Ter (c.643C>T) pathogenic?

CP p.Arg215Ter (c.643C>T) is classified Pathogenic in CP (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-29). Very rare (popmax 0.00134%, afr); Associated with aceruloplasminemia.

What condition is associated with CP p.Arg215Ter (c.643C>T)?

CP p.Arg215Ter (c.643C>T) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Arg215Ter (c.643C>T) in the general population?

CP p.Arg215Ter (c.643C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Aceruloplasminemia inherited?

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

CP p.Arg215Ter

c.643C>T · rs386134155 · VCV42122

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

aceruloplasminemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.47	loss · gain 0.09 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.4	GERP -0.91, phastCons 0.57
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,776 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,613,164 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,230
African / African-Americangrpmax	0.00134%	74,776
European (non-Finnish)	0.000593%	168,521

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg215Ter
Coding: c.643C>T
MANE Select: NM_000096
dbSNP: rs386134155
Type: single nucleotide variant
Location: chr3:149209349 (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 215: 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-arg215ter (accessed [today's date]).

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