Is CP p.Lys799Gln (c.2395A>C) pathogenic?

CP p.Lys799Gln (c.2395A>C) is classified Uncertain significance in CP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-21). AlphaMissense: likely benign (0.092); Very rare (popmax 6.85e-05%); Associated with aceruloplasminemia.

What condition is associated with CP p.Lys799Gln (c.2395A>C)?

CP p.Lys799Gln (c.2395A>C) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Lys799Gln (c.2395A>C) in the general population?

CP p.Lys799Gln (c.2395A>C) is very rare (popmax 6.85e-05%) (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.Lys799Gln (c.2395A>C)?

AlphaMissense predicts likely benign (score 0.092) — an in-silico prediction, not a clinical call.

CP p.Lys799Gln

c.2395A>C · rs2472753558 · VCV2003431

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.092 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.092	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.49	GERP 0.89
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 2.5e-07 · regional, not allelic
Overall
CADD	10.39	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,459,622 alleles · very rare

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.Lys799Gln
Coding: c.2395A>C
MANE Select: NM_000096
dbSNP: rs2472753558
Type: single nucleotide variant
Location: chr3:149183496 (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 799: the plastocyanin-like 5 domain

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

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CP p.Gly650Arg Pathogenic/Likely pathogenic ★★ same condition
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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-lys799gln (accessed [today's date]).

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