Is PEX26 p.Arg52fs (c.154del) pathogenic?

PEX26 p.Arg52fs (c.154del) is classified Pathogenic in PEX26 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-27). Very rare (popmax 0.00182%, amr); Associated with peroxisome biogenesis disorder 7A (Zellweger).

What condition is associated with PEX26 p.Arg52fs (c.154del)?

PEX26 p.Arg52fs (c.154del) is associated with peroxisome biogenesis disorder 7A (Zellweger), peroxisome biogenesis disorder 7B (ClinVar).

How common is PEX26 p.Arg52fs (c.154del) in the general population?

PEX26 p.Arg52fs (c.154del) is very rare (popmax 0.00182%, amr) (gnomAD).

PEX26 p.Arg52fs

c.154del · rs1569185857 · VCV1995469

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00182%, amr)

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 7.7	GERP 3.5, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00182% Admixed American · 1/55,094 alleles

Overall 0.000127% 2/1,577,202 alleles · very rare exomes 2/1,425,098 · genomes 0/152,104 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00182%	55,094
African / African-American	0.00135%	74,290

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.Arg52fs
Coding: c.154del
MANE Select: NM_001127649
dbSNP: rs1569185857
Type: Deletion
Location: chr22:18078529 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87

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.Arg52Gln Uncertain significance ★ ⚠ same residue
PEX26 p.Arg13fs Pathogenic ★★ same condition
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.Asp194fs 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/pex26-p-arg52fs (accessed [today's date]).

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