Is PEX26 p.Tyr299fs (c.895dup) pathogenic?

PEX26 p.Tyr299fs (c.895dup) is classified Conflicting classifications of pathogenicity in PEX26 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-02-10). Rare (popmax 0.117%, afr); Associated with PEX26-related disorder.

What condition is associated with PEX26 p.Tyr299fs (c.895dup)?

PEX26 p.Tyr299fs (c.895dup) is associated with PEX26-related disorder, peroxisome biogenesis disorder 7A (Zellweger), peroxisome biogenesis disorder 7B (ClinVar).

How common is PEX26 p.Tyr299fs (c.895dup) in the general population?

PEX26 p.Tyr299fs (c.895dup) is rare (popmax 0.117%, afr) (gnomAD).

PEX26 p.Tyr299fs

c.895dup · rs759821636 · VCV283588

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.117%, afr)

Conditions

PEX26-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP 4.1, phastCons 0.19
Overall
CADD	24.1	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 0.117% African / African-American · 88/75,034 alleles

Filtering AF 0.0975% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0901%

Overall 0.00626% 101/1,612,484 alleles · rare exomes 50/1,460,176 · genomes 51/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.117%	853
Middle Eastern	0.0165%	6,060
Admixed American	0.01%	10,005
Remaining individualsnot grpmax-eligible	0.0048%	20,821
South Asian	0.0011%	91,064
European (non-Finnish)	0.00017%	589,532

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.Tyr299fs
Coding: c.895dup
MANE Select: NM_001127649
dbSNP: rs759821636
Type: Duplication
Location: chr22:18088051 (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

PEX26-related disorder

Also linked: peroxisome biogenesis disorder 7A (Zellweger)peroxisome biogenesis disorder 7B peroxisome biogenesis disorder

Similar variants

PEX26 p.Tyr299= Likely benign ★ same residue
PEX26 p.Cys86fs Pathogenic ★★ same condition
PEX26 p.Tyr299Cys Uncertain significance ★★ ⚠ same residue
PEX26 p.Ala71fs Likely pathogenic ★ same condition
PEX26 p.Gln100fs Pathogenic ★ same condition
PEX26 p.Leu193fs Pathogenic ★ same condition
PEX26 p.Lys119fs Pathogenic ★ same condition
PEX26 p.Val181Ter 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-tyr299fs (accessed [today's date]).

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