Is PPOX p.Pro120= (c.360C>T) pathogenic?

PPOX p.Pro120= (c.360C>T) is classified Conflicting classifications of pathogenicity in PPOX (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-25). Rare (popmax 0.375%, sas); Associated with variegate porphyria.

What condition is associated with PPOX p.Pro120= (c.360C>T)?

PPOX p.Pro120= (c.360C>T) is associated with variegate porphyria (ClinVar).

How common is PPOX p.Pro120= (c.360C>T) in the general population?

PPOX p.Pro120= (c.360C>T) is rare (popmax 0.375%, sas) (gnomAD).

How is Variegate porphyria inherited?

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

PPOX p.Pro120=

c.360C>T · rs148730591 · VCV293250

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.375%, sas)

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 -3.2	GERP -3.4
Overall
CADD	5.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.375% South Asian · 342/91,082 alleles

Filtering AF 0.343% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.33%

Overall 0.0327% 528/1,614,174 alleles · rare exomes 503/1,461,892 · genomes 25/152,282 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.375%	266
Middle Eastern	0.115%	866
Remaining individualsnot grpmax-eligible	0.0384%	2,605
European (non-Finnish)	0.0127%	7,867
Admixed American	0.00666%	15,007
African / African-American	0.00133%	75,032

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: PPOX
Protein: p.Pro120=
Coding: c.360C>T
MANE Select: NM_001122764
dbSNP: rs148730591
Type: single nucleotide variant
Location: chr1:161168016 (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 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
PPOX c.-128C>G Benign/Likely benign ★★ same condition
PPOX c.-151G>T Likely benign ★★ 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-pro120 (accessed [today's date]).

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