Is CP p.Arg793Cys (c.2377C>T) pathogenic?

CP p.Arg793Cys (c.2377C>T) is classified Uncertain significance in CP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-28). AlphaMissense: likely benign (0.1159); Very rare (popmax 0.0067%, eas); Associated with aceruloplasminemia.

What condition is associated with CP p.Arg793Cys (c.2377C>T)?

CP p.Arg793Cys (c.2377C>T) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Arg793Cys (c.2377C>T) in the general population?

CP p.Arg793Cys (c.2377C>T) is very rare (popmax 0.0067%, eas) (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.Arg793Cys (c.2377C>T)?

AlphaMissense predicts likely benign (score 0.1159) — an in-silico prediction, not a clinical call.

CP p.Arg793Cys

c.2377C>T · rs771846589 · VCV2140865

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1159 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.1159	likely benign
REVEL	0.409	indeterminate
SaProt	LLR -10.28	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.48	acceptor gain · deltas
Pangolin	Δ0.42	gain · loss 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.35	GERP -4.1, phastCons 0.046
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 2.5e-07 · regional, not allelic
Overall
CADD	21.2	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 0.0067% East Asian · 3/44,802 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000869% 14/1,611,136 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0067%	14,934
South Asian	0.0044%	22,740
Admixed American	0.00334%	29,968
Remaining individualsnot grpmax-eligible	0.0016%	62,326
European (non-Finnish)	0.000339%	294,884

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.Arg793Cys
Coding: c.2377C>T
MANE Select: NM_000096
dbSNP: rs771846589
Type: single nucleotide variant
Location: chr3:149183514 (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 793: the plastocyanin-like 5 domain; a UniProt-annotated variant site (no effect on the localization at the plasma membrane)

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.Arg793His Benign/Likely benign ★★ ⚠ same residue
HPS3 p.Val793Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
HPS3 p.Val793Glu Uncertain significance ★ ⚠ same residue
HPS3 p.Val793= Likely benign ★ 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

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-arg793cys (accessed [today's date]).

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