Is PEX3 p.Ser98fs (c.292_302del) pathogenic?

PEX3 p.Ser98fs (c.292302del) is classified Pathogenic/Likely pathogenic in PEX3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-22). Ultra-rare (popmax 0.01%, amr); Associated with peroxisome biogenesis disorder 10A (Zellweger).

What condition is associated with PEX3 p.Ser98fs (c.292_302del)?

PEX3 p.Ser98fs (c.292_302del) is associated with peroxisome biogenesis disorder 10A (Zellweger) (ClinVar).

How common is PEX3 p.Ser98fs (c.292_302del) in the general population?

PEX3 p.Ser98fs (c.292_302del) is ultra-rare (popmax 0.01%, amr) (gnomAD).

PEX3 p.Ser98fs

c.292_302del · rs748689554 · VCV973435

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Conditions

peroxisome biogenesis disorder 10A (Zellweger)

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 4 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,716 alleles

Filtering AF 0.0043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.00039% 6/1,539,970 alleles · ultra-rare exomes 6/1,387,954 · genomes 0/152,016 · joint denominator

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: PEX3
Protein: p.Ser98fs
Coding: c.292_302del
MANE Select: NM_003630
dbSNP: rs748689554
Type: Deletion
Location: chr6:143468124 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB

Full PEX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 10A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX3 c.206-14del Benign ★★ same condition
PEX3 p.Met1fs Likely pathogenic ★ same condition
PEX3 p.Ser98= Likely benign ★ same residue
PEX3 c.288-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX3 c.-96G>T Uncertain significance ★★ same condition
PEX3 p.Arg300Gln Uncertain significance ★★ ⚠ same condition
PEX3 p.Asp305Glu Uncertain significance ★★ ⚠ same condition
PEX3 p.Glu266Asp Uncertain significance ★★ ⚠ 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/pex3-p-ser98fs (accessed [today's date]).

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