Is PPOX p.Pro121Ala (c.361C>G) pathogenic?

PPOX p.Pro121Ala (c.361C>G) is classified Uncertain significance in PPOX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-14). AlphaMissense: ambiguous (0.3562); Absent from gnomAD v4.1.

How common is PPOX p.Pro121Ala (c.361C>G) in the general population?

PPOX p.Pro121Ala (c.361C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPOX p.Pro121Ala (c.361C>G)?

AlphaMissense predicts ambiguous (score 0.3562) — an in-silico prediction, not a clinical call.

PPOX p.Pro121Ala

c.361C>G · rs532136485 · VCV2771314

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3562 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3562	ambiguous
REVEL	0.763	pathogenic-leaning
SaProt	LLR -12.25	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Overall
CADD	25.1	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.Pro121Ala
Coding: c.361C>G
MANE Select: NM_001122764
dbSNP: rs532136485
Type: single nucleotide variant
Location: chr1:161168017 (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.Pro121Arg Uncertain significance ★ ⚠ same residue
PPOX p.Pro121His Uncertain significance ★ ⚠ same residue
PPOX p.Pro121Thr Uncertain significance ★ ⚠ same residue
PPOX p.Pro121fs Likely pathogenic ★ 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

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-pro121ala (accessed [today's date]).

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