Is PEX1 p.Cys1102fs (c.3303_3304dup) pathogenic?

PEX1 p.Cys1102fs (c.33033304dup) is classified Pathogenic/Likely pathogenic in PEX1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-07-28). Very rare (popmax 0.000933%, nfe); Associated with peroxisome biogenesis disorder 1B.

What condition is associated with PEX1 p.Cys1102fs (c.3303_3304dup)?

PEX1 p.Cys1102fs (c.3303_3304dup) is associated with peroxisome biogenesis disorder 1B, peroxisome biogenesis disorder 1A (Zellweger), Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Cys1102fs (c.3303_3304dup) in the general population?

PEX1 p.Cys1102fs (c.3303_3304dup) is very rare (popmax 0.000933%, nfe) (gnomAD).

PEX1 p.Cys1102fs

c.3303_3304dup · rs886043558 · VCV287046

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000933%, nfe)

Conditions

peroxisome biogenesis disorder 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.3	GERP 3, phastCons 0.77

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000933% European (non-Finnish) · 11/1,179,534 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000821% 12/1,461,284 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)grpmax	0.000933%	107,230

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.Cys1102fs
Coding: c.3303_3304dup
MANE Select: NM_021167 · reported on NM_000466
dbSNP: rs886043558
Type: Duplication
Location: chr7:92491405 (GRCh38)

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

Disease context

peroxisome biogenesis disorder 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

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-cys1102fs (accessed [today's date]).

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