Is PPOX p.Arg3Gln (c.8G>A) pathogenic?

PPOX p.Arg3Gln (c.8G>A) is classified Uncertain significance in PPOX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-08). AlphaMissense: likely benign (0.1335); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PPOX p.Arg3Gln (c.8G>A)?

PPOX p.Arg3Gln (c.8G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PPOX p.Arg3Gln (c.8G>A) in the general population?

PPOX p.Arg3Gln (c.8G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PPOX p.Arg3Gln (c.8G>A)?

AlphaMissense predicts likely benign (score 0.1335) — an in-silico prediction, not a clinical call.

PPOX p.Arg3Gln

c.8G>A · rs2101841312 · VCV1425796

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1335 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1335	likely benign
REVEL	0.535	indeterminate
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Overall
CADD	25.2	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 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.2e-05% 1/1,613,562 alleles · very rare exomes 1/1,461,216 · genomes 0/152,346 · joint denominator

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.Arg3Gln
Coding: c.8G>A
MANE Select: NM_001122764
dbSNP: rs2101841312
Type: single nucleotide variant
Location: chr1:161166855 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPOX p.Ala221Thr Uncertain significance ★★ ⚠ same condition
PPOX p.Arg152His Uncertain significance ★★ ⚠ same condition
PPOX p.Arg267Cys Uncertain significance ★★ ⚠ same condition
PPOX p.Gln421His Uncertain significance ★★ ⚠ same condition
PPOX p.Glu355Asp Uncertain significance ★★ ⚠ same condition
PPOX p.Gly200Asp Uncertain significance ★★ ⚠ same condition
PPOX p.Gly51Asp Uncertain significance ★★ ⚠ same condition
PPOX p.His281Arg 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-arg3gln (accessed [today's date]).

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