Is PEX26 p.Arg13fs (c.37_38del) pathogenic?

PEX26 p.Arg13fs (c.3738del) is classified Pathogenic in PEX26 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-09). Very rare (popmax 0.00402%, afr); Associated with peroxisome biogenesis disorder 7A (Zellweger).

What condition is associated with PEX26 p.Arg13fs (c.37_38del)?

PEX26 p.Arg13fs (c.37_38del) is associated with peroxisome biogenesis disorder 7A (Zellweger), peroxisome biogenesis disorder 7B (ClinVar).

How common is PEX26 p.Arg13fs (c.37_38del) in the general population?

PEX26 p.Arg13fs (c.37_38del) is very rare (popmax 0.00402%, afr) (gnomAD).

PEX26 p.Arg13fs

c.37_38del · rs61752130 · VCV2925654

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Conditions

peroxisome biogenesis disorder 7A (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 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.079	GERP -4.6
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00402% African / African-American · 3/74,574 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000188% 3/1,594,592 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: PEX26
Protein: p.Arg13fs
Coding: c.37_38del
MANE Select: NM_001127649
dbSNP: rs61752130
Type: Deletion
Location: chr22:18078413 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87
Residue 13: the 'disordered' region

Full PEX26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 7A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 7B

Similar variants

PEX26 p.Arg13Met Uncertain significance ★★ ⚠ same residue
PEX26 p.Arg13= Likely benign ★ same residue
PEX26 p.Gln205fs Pathogenic ★★ same condition
PEX26 p.Leu12fs Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Tyr110fs Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Val120fs Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Ala10fs Pathogenic ★ same condition
PEX26 p.Arg52fs 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/pex26-p-arg13fs (accessed [today's date]).

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