Is EPX p.Trp53Ter (c.158G>A) pathogenic?

EPX p.Trp53Ter (c.158G>A) is classified Uncertain significance in EPX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-29). Rare (popmax 0.284%, sas); Associated with eosinophil peroxidase deficiency.

What condition is associated with EPX p.Trp53Ter (c.158G>A)?

EPX p.Trp53Ter (c.158G>A) is associated with eosinophil peroxidase deficiency (ClinVar).

How common is EPX p.Trp53Ter (c.158G>A) in the general population?

EPX p.Trp53Ter (c.158G>A) is rare (popmax 0.284%, sas) (gnomAD).

EPX p.Trp53Ter

c.158G>A · VCV3779621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.284%, sas)

Conditions

eosinophil peroxidase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.25	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.89	GERP -4.3
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.284% South Asian · 258/91,002 alleles

Filtering AF 0.255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.244%

Overall 0.0171% 275/1,609,910 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.284%	353
Remaining individualsnot grpmax-eligible	0.0256%	3,899
East Asian	0.00223%	44,860

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: EPX
Protein: p.Trp53Ter
Coding: c.158G>A
MANE Select: NM_000502
Type: single nucleotide variant
Location: chr17:58193119 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.40 · 1 PDB

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

Disease context

eosinophil peroxidase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EPX c.801+1G>A Likely benign ★★ same condition
EPX c.170+5A>G Likely benign ★★ same type
EPX c.464+8C>T Benign ★★ same type
EPX p.Asn572Tyr Benign ★★ same type
EPX p.Cys257Ter Benign ★★ same type
EPX p.Leu624= Benign/Likely benign ★★ same type
EPX p.Phe308Leu Likely benign ★★ ⚠ same type
EPX p.Pro292Leu Benign ★★ 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/epx-p-trp53ter (accessed [today's date]).

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