Is PEX5 p.Ser464= (c.1392T>C) pathogenic?

PEX5 p.Ser464= (c.1392T>C) is classified Likely benign in PEX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-31). Very rare (popmax 8.51e-05%, nfe); Associated with peroxisome biogenesis disorder 2B.

What condition is associated with PEX5 p.Ser464= (c.1392T>C)?

PEX5 p.Ser464= (c.1392T>C) is associated with peroxisome biogenesis disorder 2B (ClinVar).

How common is PEX5 p.Ser464= (c.1392T>C) in the general population?

PEX5 p.Ser464= (c.1392T>C) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

PEX5 p.Ser464=

c.1392T>C · rs2136238346 · VCV1134510

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

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 -3.9	GERP -2.6
Overall
CADD	0.528	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,174,476 alleles

Overall 6.22e-05% 1/1,607,868 alleles · very rare exomes 1/1,455,632 · genomes 0/152,236 · joint denominator

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: PEX5
Protein: p.Ser464=
Coding: c.1392T>C
MANE Select: NM_001351132
dbSNP: rs2136238346
Type: single nucleotide variant
Location: chr12:7208667 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB
Residue 464: 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.Ser464Phe 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
PEX5 p.Arg276Ter Pathogenic/Likely pathogenic ★★ same condition
PEX5 p.Arg420Ter 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-ser464 (accessed [today's date]).

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