Is PEX1 p.Asn452fs (c.1351_1354dup) pathogenic?

PEX1 p.Asn452fs (c.13511354dup) is classified Likely pathogenic in PEX1 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-05-24). Ultra-rare (gnomAD MAF 7.217e-07); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX1 p.Asn452fs (c.1351_1354dup)?

PEX1 p.Asn452fs (c.1351_1354dup) is associated with peroxisome biogenesis disorder, Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Asn452fs (c.1351_1354dup) in the general population?

PEX1 p.Asn452fs (c.1351_1354dup) is ultra-rare (gnomAD MAF 7.217e-07) (gnomAD).

PEX1 p.Asn452fs

c.1351_1354dup · rs1792596054 · VCV929187

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.217e-07)

Conditions

peroxisome biogenesis disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.48	GERP 0.58, phastCons 0.93

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

Population frequency

dbSNP / gnomAD

Global frequency 7.22e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: PEX1
Protein: p.Asn452fs
Coding: c.1351_1354dup
MANE Select: NM_000466
dbSNP: rs1792596054
Type: Microsatellite
Location: chr7:92513852 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19

Full PEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Zellweger spectrum disorders

Similar variants

PEX1 p.Asn452His Uncertain significance ★ ⚠ same residue
PEX1 c.1671_1672del Pathogenic ★★ same condition
PEX1 p.Arg798fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Gln1231fs Pathogenic ★★ same condition
PEX1 p.Glu897_Ser898insTer Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.His572fs Pathogenic ★★ same condition
PEX1 p.His678fs Pathogenic ★★ same condition
PEX1 p.Ile528fs Pathogenic/Likely pathogenic ★★ 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/pex1-p-asn452fs (accessed [today's date]).

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