Is PEX13 p.Pro8fs (c.20dup) pathogenic?

PEX13 p.Pro8fs (c.20dup) is classified Pathogenic in PEX13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-30). Very rare (popmax 8.72e-05%, nfe); Associated with peroxisome biogenesis disorder 11A (Zellweger).

What condition is associated with PEX13 p.Pro8fs (c.20dup)?

PEX13 p.Pro8fs (c.20dup) is associated with peroxisome biogenesis disorder 11A (Zellweger) (ClinVar).

How common is PEX13 p.Pro8fs (c.20dup) in the general population?

PEX13 p.Pro8fs (c.20dup) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

PEX13 p.Pro8fs

c.20dup · rs2467473532 · VCV2805185

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Conditions

peroxisome biogenesis disorder 11A (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 1 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.069	GERP -3, phastCons 0.19

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,146,628 alleles

Overall 7.16e-05% 1/1,397,484 alleles · very rare

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: PEX13
Protein: p.Pro8fs
Coding: c.20dup
MANE Select: NM_002618
dbSNP: rs2467473532
Type: Duplication
Location: chr2:61017777 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.62 · 3 PDB
Residue 8: the 'disordered' region

Full PEX13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 11A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX13 p.Pro8Leu Uncertain significance ★ same residue
PEX13 p.Ala277fs Pathogenic ★ same condition
PEX13 p.Thr49fs Pathogenic ★ same condition
PEX13 p.Val68fs Pathogenic ★ same condition
PEX13 c.914-8dup Benign ★ same condition
PEX13 c.93-3dup Likely benign ★ same condition
PEX13 p.Pro8= Likely benign ★ same residue
PEX13 p.Arg16Ter 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/pex13-p-pro8fs (accessed [today's date]).

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