Is PPOX p.Arg23= (c.69G>T) pathogenic?

PPOX p.Arg23= (c.69G>T) is classified Uncertain significance in PPOX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Absent from gnomAD v4.1; Associated with variegate porphyria.

What condition is associated with PPOX p.Arg23= (c.69G>T)?

PPOX p.Arg23= (c.69G>T) is associated with variegate porphyria (ClinVar).

How common is PPOX p.Arg23= (c.69G>T) in the general population?

PPOX p.Arg23= (c.69G>T) is absent from gnomAD v4.1 (gnomAD).

How is Variegate porphyria inherited?

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

PPOX p.Arg23=

c.69G>T · rs886045452 · VCV293247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

variegate porphyria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -2.8, phastCons 1
Overall
CADD	8.347	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPOX
Protein: p.Arg23=
Coding: c.69G>T
MANE Select: NM_001122764
dbSNP: rs886045452
Type: single nucleotide variant
Location: chr1:161166916 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.24 (gnomAD)
Structure: AlphaFold pLDDT 95.39 · 3 PDB

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

Disease context

variegate porphyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Variegate porphyria (Orphanet):

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

Similar variants

PPOX p.Arg23Trp Uncertain significance ★★ ⚠ same residue
PPOX p.Arg23Gln Likely benign ★ same residue
PPOX c.-9G>A Likely pathogenic ★★ same condition
PPOX p.Arg168His Pathogenic/Likely pathogenic ★★ ⚠ same condition
PPOX p.Arg59Trp Pathogenic ★★ same condition
PPOX p.Ala449Thr Uncertain significance ★★ ⚠ same condition
PPOX p.Arg267Cys Uncertain significance ★★ ⚠ same condition
PPOX p.Pro407Leu 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/ppox-p-arg23 (accessed [today's date]).

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