Is CP p.Arg367Cys (c.1099C>T) pathogenic?

CP p.Arg367Cys (c.1099C>T) is classified Benign/Likely benign in CP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0921); Low-frequency (popmax 4.45%, afr); Associated with aceruloplasminemia.

What condition is associated with CP p.Arg367Cys (c.1099C>T)?

CP p.Arg367Cys (c.1099C>T) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Arg367Cys (c.1099C>T) in the general population?

CP p.Arg367Cys (c.1099C>T) is low-frequency (popmax 4.45%, 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.Arg367Cys (c.1099C>T)?

AlphaMissense predicts likely benign (score 0.0921) — an in-silico prediction, not a clinical call.

CP p.Arg367Cys

c.1099C>T · rs34624984 · VCV128837

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0921 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.45%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.0921	likely benign
REVEL	0.388	indeterminate
SaProt	LLR -8.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.32	GERP -3.1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.56 · regional, not allelic
Overall
CADD	15.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.45% African / African-American · 3,335/74,988 alleles

Filtering AF 4.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.27%

Overall 0.254% 4,107/1,613,912 alleles · low-frequency exomes 2,059/1,461,736 · genomes 2,048/152,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.45%	22
Admixed American	0.46%	217
Remaining individualsnot grpmax-eligible	0.347%	288
Middle Eastern	0.297%	337
European (non-Finnish)	0.0208%	4,796
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,920
South Asian	0.00988%	10,119
Finnishnot grpmax-eligible	0.00156%	64,026

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.Arg367Cys
Coding: c.1099C>T
MANE Select: NM_000096
dbSNP: rs34624984
Type: single nucleotide variant
Location: chr3:149206277 (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 367: a β-strand; a UniProt-annotated variant site (in)

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.Arg367His Conflicting classifications of pathogenicity ★ ⚠ same residue
CP p.Arg367Leu Uncertain significance ★ ⚠ 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-arg367cys (accessed [today's date]).

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