Is PAOX p.Arg495Cys (c.1483C>T) pathogenic?

PAOX p.Arg495Cys (c.1483C>T) is classified Uncertain significance in PAOX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: ambiguous (0.4049); Rare (popmax 0.463%, eas).

How common is PAOX p.Arg495Cys (c.1483C>T) in the general population?

PAOX p.Arg495Cys (c.1483C>T) is rare (popmax 0.463%, eas) (gnomAD).

What do computational predictors say about PAOX p.Arg495Cys (c.1483C>T)?

AlphaMissense predicts ambiguous (score 0.4049) — an in-silico prediction, not a clinical call.

PAOX p.Arg495Cys

c.1483C>T · rs200635963 · VCV2539905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4049 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.463%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4049	ambiguous
REVEL	0.757	pathogenic-leaning
SaProt	LLR -12.87	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 12 kb · p 0.48 · regional, not allelic
Overall
CADD	28.8	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 0.463% East Asian · 208/44,884 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.392%

Overall 0.0142% 229/1,613,046 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.463%	216
Remaining individualsnot grpmax-eligible	0.0048%	20,832
European (non-Finnish)	0.00136%	73,750
African / African-American	0.00133%	75,054
South Asian	0.0011%	91,070

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.Arg495Cys
Coding: c.1483C>T
MANE Select: NM_152911
dbSNP: rs200635963
Type: single nucleotide variant
Location: chr10:133391402 (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.Arg495His Uncertain significance ★ ⚠ same residue
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

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-arg495cys (accessed [today's date]).

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