Is PAOX p.Pro502= (c.1506G>A) pathogenic?

PAOX p.Pro502= (c.1506G>A) is classified Likely benign in PAOX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). Rare (popmax 0.115%, mid).

How common is PAOX p.Pro502= (c.1506G>A) in the general population?

PAOX p.Pro502= (c.1506G>A) is rare (popmax 0.115%, mid) (gnomAD).

PAOX p.Pro502=

c.1506G>A · VCV4564381

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.067	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2
Overall
CADD	1.701	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.00335% 54/1,612,512 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	866
European (non-Finnish)	0.00347%	28,777
Remaining individualsnot grpmax-eligible	0.0032%	31,247
African / African-American	0.00267%	37,515
Admixed American	0.00167%	59,994
South Asian	0.0011%	91,050

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: PAOX
Protein: p.Pro502=
Coding: c.1506G>A
MANE Select: NM_152911
Type: single nucleotide variant
Location: chr10:133391425 (GRCh38)
Gene constraint: LOEUF 1.292 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.77

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

Similar variants

PAOX p.Glu329Asp Uncertain significance ★★ ⚠ same type
PAOX p.Ala116Ser Uncertain significance ★ ⚠ same type
PAOX p.Ala128Val Uncertain significance ★ ⚠ same type
PAOX p.Ala131Gly Uncertain significance ★ ⚠ same type
PAOX p.Ala235Thr Uncertain significance ★ ⚠ same type
PAOX p.Arg277Trp Uncertain significance ★ ⚠ same type
PAOX p.Arg415Trp Uncertain significance ★ ⚠ same type
PAOX p.Arg424Gln 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/paox-p-pro502 (accessed [today's date]).

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