Is PPOX p.Ala93Val (c.278C>T) pathogenic?

PPOX p.Ala93Val (c.278C>T) is classified Uncertain significance in PPOX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: ambiguous (0.4051); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with PPOX p.Ala93Val (c.278C>T)?

PPOX p.Ala93Val (c.278C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PPOX p.Ala93Val (c.278C>T) in the general population?

PPOX p.Ala93Val (c.278C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PPOX p.Ala93Val (c.278C>T)?

AlphaMissense predicts ambiguous (score 0.4051) — an in-silico prediction, not a clinical call.

PPOX p.Ala93Val

c.278C>T · rs2525202835 · VCV2244906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4051 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4051	ambiguous
REVEL	0.691	pathogenic-leaning
SaProt	LLR -9.88	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Overall
CADD	28.5	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

Grpmax group 0.0011% South Asian · 1/91,062 alleles

Overall 6.2e-05% 1/1,613,754 alleles · very rare exomes 1/1,461,514 · genomes 0/152,240 · 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.Ala93Val
Coding: c.278C>T
MANE Select: NM_001122764
dbSNP: rs2525202835
Type: single nucleotide variant
Location: chr1:161167426 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.24 (gnomAD)
Structure: AlphaFold pLDDT 95.39 · 3 PDB
Residue 93: an α-helix

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.Arg3Gln 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

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-ala93val (accessed [today's date]).

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