Is PEX26 p.Asp147= (c.441C>T) pathogenic?

PEX26 p.Asp147= (c.441C>T) is classified Conflicting classifications of pathogenicity in PEX26 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0883%, amr); Associated with peroxisome biogenesis disorder 7B.

What condition is associated with PEX26 p.Asp147= (c.441C>T)?

PEX26 p.Asp147= (c.441C>T) is associated with peroxisome biogenesis disorder 7B, peroxisome biogenesis disorder 7A (Zellweger) (ClinVar).

How common is PEX26 p.Asp147= (c.441C>T) in the general population?

PEX26 p.Asp147= (c.441C>T) is ultra-rare (popmax 0.0883%, amr) (gnomAD).

PEX26 p.Asp147=

c.441C>T · rs770611373 · VCV502759

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0883%, amr)

Conditions

peroxisome biogenesis disorder 7B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.26	GERP 0.91
Overall
CADD	5.482	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0883% Admixed American · 53/59,998 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0626%

Overall 0.00335% 54/1,613,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0883%	1,132
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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.Asp147=
Coding: c.441C>T
MANE Select: NM_001127649
dbSNP: rs770611373
Type: single nucleotide variant
Location: chr22:18083506 (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 7B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 7A (Zellweger)

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-asp147 (accessed [today's date]).

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