Is PEX26 p.Arg268= (c.804A>G) pathogenic?

PEX26 p.Arg268= (c.804A>G) is classified Likely benign in PEX26 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). Very rare (popmax 0.00401%, afr); Associated with peroxisome biogenesis disorder 7A (Zellweger).

What condition is associated with PEX26 p.Arg268= (c.804A>G)?

PEX26 p.Arg268= (c.804A>G) is associated with peroxisome biogenesis disorder 7A (Zellweger), peroxisome biogenesis disorder 7B (ClinVar).

How common is PEX26 p.Arg268= (c.804A>G) in the general population?

PEX26 p.Arg268= (c.804A>G) is very rare (popmax 0.00401%, afr) (gnomAD).

PEX26 p.Arg268=

c.804A>G · rs1055672932 · VCV1411263

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

peroxisome biogenesis disorder 7A (Zellweger)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.74 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.1	GERP 0.63, phastCons 1
Overall
CADD	7.584	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,834 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,790 alleles · very rare exomes 0/1,461,822 · genomes 4/151,968 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,945
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Arg268=
Coding: c.804A>G
MANE Select: NM_001127649
dbSNP: rs1055672932
Type: single nucleotide variant
Location: chr22:18085248 (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 c.230+1G>T Pathogenic ★★ same condition
PEX26 c.667+2T>C Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Arg98Trp Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Gln146Ter Pathogenic ★★ same condition
PEX26 p.Gly89Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
PEX26 p.Trp62Ter Pathogenic/Likely pathogenic ★★ same condition
PEX26 c.230+3A>G 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/pex26-p-arg268 (accessed [today's date]).

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