Is CP p.Arg793His (c.2378G>A) pathogenic?

CP p.Arg793His (c.2378G>A) is classified Benign/Likely benign in CP (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0712); Low-frequency (popmax 1.87%, afr); Associated with aceruloplasminemia.

What condition is associated with CP p.Arg793His (c.2378G>A)?

CP p.Arg793His (c.2378G>A) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Arg793His (c.2378G>A) in the general population?

CP p.Arg793His (c.2378G>A) is low-frequency (popmax 1.87%, 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.Arg793His (c.2378G>A)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

CP p.Arg793His

c.2378G>A · rs115552500 · VCV128839

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.87%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -8.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.9	GERP -4.1
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 2.5e-07 · regional, not allelic
Overall
CADD	14.29	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 1.87% African / African-American · 1,397/74,766 alleles

Filtering AF 1.79% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.75%

Overall 0.991% 15,971/1,611,260 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.84%	26
African / African-Americangrpmax	1.87%	54
Middle Eastern	1.37%	73
European (non-Finnish)	1.08%	93
Remaining individualsnot grpmax-eligible	1.05%	95
Admixed American	0.87%	115
Ashkenazi Jewishnot grpmax-eligible	0.585%	171
South Asian	0.311%	321
Finnishnot grpmax-eligible	0.14%	715
East Asian	0.00446%	22,406

Amish 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.Arg793His
Coding: c.2378G>A
MANE Select: NM_000096
dbSNP: rs115552500
Type: single nucleotide variant
Location: chr3:149183513 (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.Arg793Cys Uncertain significance ★★ ⚠ 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-arg793his (accessed [today's date]).

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