Is PEX5 p.Pro42= (c.126C>T) pathogenic?

PEX5 p.Pro42= (c.126C>T) is classified Likely benign in PEX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder 2B.

What condition is associated with PEX5 p.Pro42= (c.126C>T)?

PEX5 p.Pro42= (c.126C>T) is associated with peroxisome biogenesis disorder 2B (ClinVar).

How common is PEX5 p.Pro42= (c.126C>T) in the general population?

PEX5 p.Pro42= (c.126C>T) is absent from gnomAD v4.1 (gnomAD).

PEX5 p.Pro42=

c.126C>T · rs1199646327 · VCV741209

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

peroxisome biogenesis disorder 2B

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 -4.2	GERP -2.7
Overall
CADD	0.932	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEX5
Protein: p.Pro42=
Coding: c.126C>T
MANE Select: NM_001351132
dbSNP: rs1199646327
Type: single nucleotide variant
Location: chr12:7190503 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB
Residue 42: the 'disordered' region

Full PEX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 2B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX5 p.Pro42Ala Uncertain significance ★ ⚠ same residue
PEX5 p.Pro42Arg Uncertain significance ★ ⚠ same residue
PEX5 p.Pro42Leu Uncertain significance ★ ⚠ same residue
PEX5 c.449-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX5 c.552-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX5 c.847-2A>G Likely pathogenic ★★ same condition
PEX5 c.967-1G>A Likely pathogenic ★★ same condition
PEX5 p.Arg237Ter Pathogenic/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/pex5-p-pro42 (accessed [today's date]).

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