Is CPOX p.Gln29Pro (c.86A>C) pathogenic?

CPOX p.Gln29Pro (c.86A>C) is classified Uncertain significance in CPOX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.0467); Very rare (popmax 0.00587%, eas); Associated with hereditary coproporphyria.

What condition is associated with CPOX p.Gln29Pro (c.86A>C)?

CPOX p.Gln29Pro (c.86A>C) is associated with hereditary coproporphyria (ClinVar).

How common is CPOX p.Gln29Pro (c.86A>C) in the general population?

CPOX p.Gln29Pro (c.86A>C) is very rare (popmax 0.00587%, eas) (gnomAD).

How is Hereditary coproporphyria inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CPOX p.Gln29Pro (c.86A>C)?

AlphaMissense predicts likely benign (score 0.0467) — an in-silico prediction, not a clinical call.

CPOX p.Gln29Pro

c.86A>C · rs886058952 · VCV346995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0467 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00587%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary coproporphyria

Computational evidence

Protein change
AlphaMissense	0.0467	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -6.03	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 -0.6	GERP -1.3, phastCons 0.001
Regional constraint	o/e 1.06	unconstrained · MANE · 2,476 bp · p 0.32 · regional, not allelic
Overall
CADD	2.883	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 0.00587% East Asian · 2/34,080 alleles

Filtering AF 0.000972% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000364%

Overall 0.000153% 2/1,305,362 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: CPOX
Protein: p.Gln29Pro
Coding: c.86A>C
MANE Select: NM_000097
dbSNP: rs886058952
Type: single nucleotide variant
Location: chr3:98593419 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 1 PDB
Residue 29: a UniProt-annotated variant site (in hcp)

Full CPOX gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary coproporphyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary coproporphyria (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

CPOX p.Gln29His Uncertain significance ★ ⚠ same residue
CPOX p.Gln29= Likely benign ★ same residue
CPOX p.Gln29Ter Pathogenic same residue
CPOX p.Gln160Ter Pathogenic ★★ same condition
CPOX p.Glu201Lys Pathogenic/Likely pathogenic ★★ same condition
CPOX p.Lys404Glu Pathogenic/Likely pathogenic ★★ same condition
CPOX p.Arg60Gly Uncertain significance ★★ ⚠ same condition
CPOX p.Thr56Met Uncertain significance ★★ ⚠ 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/cpox-p-gln29pro (accessed [today's date]).

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