Is PPOX p.Leu85Pro (c.254T>C) pathogenic?

PPOX p.Leu85Pro (c.254T>C) is classified Likely pathogenic in PPOX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: likely pathogenic (0.9657); Absent from gnomAD v4.1.

How common is PPOX p.Leu85Pro (c.254T>C) in the general population?

PPOX p.Leu85Pro (c.254T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPOX p.Leu85Pro (c.254T>C)?

AlphaMissense predicts likely pathogenic (score 0.9657) — an in-silico prediction, not a clinical call.

PPOX p.Leu85Pro

c.254T>C · rs910986823 · VCV1472461

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9657 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9657	likely pathogenic ✓ concordant with ClinVar · top 5% in PPOX
REVEL	0.913	moderately pathogenic-leaning
SaProt	LLR -14.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Overall
CADD	29.0	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.Leu85Pro
Coding: c.254T>C
MANE Select: NM_001122764
dbSNP: rs910986823
Type: single nucleotide variant
Location: chr1:161167402 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.24 (gnomAD)
Structure: AlphaFold pLDDT 95.39 · 3 PDB
Residue 85: a UniProt-annotated variant site (in vp; abolishes enzyme activity; impairs protein folding and/or stability); a β-strand

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

Similar variants

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
PPOX p.Glu133Ter Pathogenic ★★ same type
PPOX p.Glu191Ter Pathogenic/Likely pathogenic ★★ same type
PPOX c.471+3G>A Uncertain significance ★★ 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-leu85pro (accessed [today's date]).

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