Is PEX5 p.Arg427fs (c.1279dup) pathogenic?

PEX5 p.Arg427fs (c.1279dup) is classified Pathogenic in PEX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). No gnomAD frequency available for this variant; Associated with peroxisome biogenesis disorder 2B.

What condition is associated with PEX5 p.Arg427fs (c.1279dup)?

PEX5 p.Arg427fs (c.1279dup) is associated with peroxisome biogenesis disorder 2B (ClinVar).

How common is PEX5 p.Arg427fs (c.1279dup) in the general population?

PEX5 p.Arg427fs (c.1279dup) is no gnomAD frequency available for this variant (gnomAD).

PEX5 p.Arg427fs

c.1279dup · rs759789707 · VCV2769438

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

peroxisome biogenesis disorder 2B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP -0.31, phastCons 0.99

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PEX5
Protein: p.Arg427fs
Coding: c.1279dup
MANE Select: NM_001351132
dbSNP: rs759789707
Type: Duplication
Location: chr12:7208553 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB
Residue 427: a UniProt-annotated variant site (in pbd2b; impaired ability to mediate peroxisomal import of proteins containing both a c-terminal pts1- and pts2-type targeting signals); an α-helix

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.Arg427Ter Pathogenic ★★ same residue
PEX5 p.Arg427Gln Uncertain significance ★★ ⚠ same residue
PEX5 p.Arg427Leu Uncertain significance ★★ same residue
PEX5 p.Ser235fs Pathogenic/Likely pathogenic ★★ same condition
PEX5 p.Thr316fs Pathogenic/Likely pathogenic ★★ same condition
PEX5 c.967-3dup Uncertain significance ★★ same condition
PEX5 c.1718+11_1718+14dup Likely benign ★★ same condition
PEX5 p.Ala422fs 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-arg427fs (accessed [today's date]).

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