Is CP p.Gly895Ala (c.2684G>C) pathogenic?

CP p.Gly895Ala (c.2684G>C) is classified Conflicting classifications of pathogenicity in CP (ClinVar, Conflicting submitters, 18 submitters; last evaluated 2026-09-10). AlphaMissense: ambiguous (0.555); Rare (popmax 0.28%, amr); Associated with aceruloplasminemia.

What condition is associated with CP p.Gly895Ala (c.2684G>C)?

CP p.Gly895Ala (c.2684G>C) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Gly895Ala (c.2684G>C) in the general population?

CP p.Gly895Ala (c.2684G>C) is rare (popmax 0.28%, amr) (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.Gly895Ala (c.2684G>C)?

AlphaMissense predicts ambiguous (score 0.555) — an in-silico prediction, not a clinical call.

CP p.Gly895Ala

c.2684G>C · rs139633388 · VCV42054

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 18 submitters

AlphaMissense

ambiguous

0.555 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.28%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.555	ambiguous
REVEL	0.947	strongly pathogenic-leaning
SaProt	LLR -9.53	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 2.5e-07 · 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 0.28% Admixed American · 168/59,932 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.232%

Overall 0.182% 2,940/1,611,726 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.28%	357
European (non-Finnish)	0.213%	469
Remaining individualsnot grpmax-eligible	0.179%	557
Ashkenazi Jewishnot grpmax-eligible	0.125%	799
Finnishnot grpmax-eligible	0.119%	839
Middle Eastern	0.033%	3,030
African / African-American	0.0294%	3,402
South Asian	0.0077%	12,993
East Asian	0.00223%	44,810

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.Gly895Ala
Coding: c.2684G>C
MANE Select: NM_000096
dbSNP: rs139633388
Type: single nucleotide variant
Location: chr3:149178609 (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 895: a β-strand; the plastocyanin-like 5 domain; a disulfide bond

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.Gly895= 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
CP p.Gly650Arg Pathogenic/Likely pathogenic ★★ same condition
CP p.Gly708Ser Pathogenic ★★ same condition
CP p.Leu919Pro Pathogenic/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-gly895ala (accessed [today's date]).

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