Is CP p.Asn263Ser (c.788A>G) pathogenic?

CP p.Asn263Ser (c.788A>G) is classified Conflicting classifications of pathogenicity in CP (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-02-28). AlphaMissense: ambiguous (0.4732); Rare (popmax 0.165%, mid); Associated with aceruloplasminemia.

What condition is associated with CP p.Asn263Ser (c.788A>G)?

CP p.Asn263Ser (c.788A>G) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Asn263Ser (c.788A>G) in the general population?

CP p.Asn263Ser (c.788A>G) is rare (popmax 0.165%, mid) (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.Asn263Ser (c.788A>G)?

AlphaMissense predicts ambiguous (score 0.4732) — an in-silico prediction, not a clinical call.

CP p.Asn263Ser

c.788A>G · rs150303869 · VCV343782

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

ambiguous

0.4732 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.165%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.4732	ambiguous
REVEL	0.809	moderately pathogenic-leaning
SaProt	LLR -13.05	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.56 · regional, not allelic
Overall
CADD	25.6	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 0.165% Middle Eastern · 10/6,062 alleles

Filtering AF 0.0895% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0681%

Overall 0.0512% 827/1,613,904 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.165%	606
European (non-Finnish)	0.0623%	1,605
Finnishnot grpmax-eligible	0.039%	2,561
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Admixed American	0.0217%	4,616
South Asian	0.0165%	6,072
African / African-American	0.00666%	15,008

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.Asn263Ser
Coding: c.788A>G
MANE Select: NM_000096
dbSNP: rs150303869
Type: single nucleotide variant
Location: chr3:149207611 (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 263: the plastocyanin-like 2 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

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
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-asn263ser (accessed [today's date]).

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