Is CP p.Gly347Ser (c.1039G>A) pathogenic?

CP p.Gly347Ser (c.1039G>A) is classified Uncertain significance in CP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-03). AlphaMissense: ambiguous (0.5247); Very rare (popmax 0.00446%, eas); Associated with aceruloplasminemia.

What condition is associated with CP p.Gly347Ser (c.1039G>A)?

CP p.Gly347Ser (c.1039G>A) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Gly347Ser (c.1039G>A) in the general population?

CP p.Gly347Ser (c.1039G>A) is very rare (popmax 0.00446%, 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.Gly347Ser (c.1039G>A)?

AlphaMissense predicts ambiguous (score 0.5247) — an in-silico prediction, not a clinical call.

CP p.Gly347Ser

c.1039G>A · rs761317252 · VCV1524833

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5247 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.5247	ambiguous
REVEL	0.906	moderately pathogenic-leaning
SaProt	LLR -11.62	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.48	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.56 · regional, not allelic
Overall
CADD	29.9	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 0.00446% East Asian · 2/44,854 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000821% 12/1,461,582 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,427
South Asian	0.0022%	45,528
African / African-American	0.00133%	74,962
European (non-Finnish)	0.000593%	168,536

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.Gly347Ser
Coding: c.1039G>A
MANE Select: NM_000096
dbSNP: rs761317252
Type: single nucleotide variant
Location: chr3:149206337 (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 347: a turn; the plastocyanin-like 2 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.Gly347Asp Likely pathogenic ★ same residue
CP p.Gly347Arg Uncertain significance ★ ⚠ 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

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-gly347ser (accessed [today's date]).

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