Is PEX1 p.Leu1024fs (c.3070_3071del) pathogenic?

PEX1 p.Leu1024fs (c.30703071del) is classified Pathogenic/Likely pathogenic in PEX1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-27). Very rare (popmax 0.000424%, nfe); Associated with Heimler syndrome 1.

What condition is associated with PEX1 p.Leu1024fs (c.3070_3071del)?

PEX1 p.Leu1024fs (c.3070_3071del) is associated with Heimler syndrome 1, peroxisome biogenesis disorder 1A (Zellweger), peroxisome biogenesis disorder 1B (ClinVar).

How common is PEX1 p.Leu1024fs (c.3070_3071del) in the general population?

PEX1 p.Leu1024fs (c.3070_3071del) is very rare (popmax 0.000424%, nfe) (gnomAD).

PEX1 p.Leu1024fs

c.3070_3071del · rs1312351030 · VCV861041

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

Heimler syndrome 1

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 20 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.7	GERP -5.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,178,552 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000411% 6/1,460,156 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,430
European (non-Finnish)grpmax	0.000424%	235,711

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PEX1
Protein: p.Leu1024fs
Coding: c.3070_3071del
MANE Select: NM_000466
dbSNP: rs1312351030
Type: Microsatellite
Location: chr7:92493089 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 1024: a UniProt-annotated variant site (in pbd1a)

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

Disease context

Heimler syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 1A (Zellweger)peroxisome biogenesis disorder 1B Zellweger spectrum disorders

Similar variants

PEX1 p.Leu1024= Likely benign ★ 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-leu1024fs (accessed [today's date]).

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