Is PPOX p.Pro28Leu (c.83C>T) pathogenic?

PPOX p.Pro28Leu (c.83C>T) is classified Uncertain significance in PPOX (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-16). AlphaMissense: likely benign (0.1833); Absent from gnomAD v4.1.

How common is PPOX p.Pro28Leu (c.83C>T) in the general population?

PPOX p.Pro28Leu (c.83C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPOX p.Pro28Leu (c.83C>T)?

AlphaMissense predicts likely benign (score 0.1833) — an in-silico prediction, not a clinical call.

PPOX p.Pro28Leu

c.83C>T · rs374585133 · VCV961039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1833 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1833	likely benign
REVEL	0.611	indeterminate
SaProt	LLR -13.56	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.4, phastCons 1
Overall
CADD	24.4	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

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.Pro28Leu
Coding: c.83C>T
MANE Select: NM_001122764
dbSNP: rs374585133
Type: single nucleotide variant
Location: chr1:161166930 (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

Similar variants

PPOX p.Pro28Ala Uncertain significance ★★ ⚠ same residue
PPOX p.Pro28Thr Uncertain significance ★★ ⚠ same residue
PPOX p.Pro28Arg Uncertain significance ★ ⚠ same residue
PPOX c.-9G>A Likely pathogenic ★★ same type
PPOX p.Arg168His Pathogenic/Likely pathogenic ★★ ⚠ same type
PPOX p.Arg59Trp Pathogenic ★★ same type
PPOX p.Gln189Ter Pathogenic ★★ same type
PPOX p.Gln435Ter Pathogenic/Likely pathogenic ★★ same type

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-pro28leu (accessed [today's date]).

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