Is CP p.Arg367His (c.1100G>A) pathogenic?

CP p.Arg367His (c.1100G>A) is classified Conflicting classifications of pathogenicity in CP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-08-20). AlphaMissense: likely benign (0.0608); Ultra-rare (popmax 0.0134%, afr); Associated with aceruloplasminemia.

What condition is associated with CP p.Arg367His (c.1100G>A)?

CP p.Arg367His (c.1100G>A) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Arg367His (c.1100G>A) in the general population?

CP p.Arg367His (c.1100G>A) is ultra-rare (popmax 0.0134%, 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.Arg367His (c.1100G>A)?

AlphaMissense predicts likely benign (score 0.0608) — an in-silico prediction, not a clinical call.

CP p.Arg367His

c.1100G>A · VCV3379507

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0608 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.0608	likely benign
REVEL	0.316	indeterminate
SaProt	LLR -6.43	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 -20	GERP -4.4
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.56 · regional, not allelic
Overall
CADD	0.001	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 0.0134% African / African-American · 10/74,890 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00167% 27/1,613,828 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,489
Admixed American	0.00667%	14,997
East Asian	0.00223%	44,872
European (non-Finnish)	0.00102%	98,325

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.Arg367His
Coding: c.1100G>A
MANE Select: NM_000096
Type: single nucleotide variant
Location: chr3:149206276 (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.Arg367Cys Benign/Likely benign ★★ ⚠ 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-arg367his (accessed [today's date]).

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