PEX5 p.Arg593=
c.1777C>A · rs144333076 · VCV2121939
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
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 3.2 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 11.61 | 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.Arg593=
- Coding
- c.1777C>A
- MANE Select
- NM_001351132
- dbSNP
- rs144333076
- Type
- single nucleotide variant
- Location
- chr12:7210080 (GRCh38)
- Gene constraint
- LOEUF 0.768 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.28 · 11 PDB
- Residue 593
- 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); a β-strand
Similar variants
- PEX5 p.Arg593Trp Uncertain significance ★★ ⚠ same residue
- PEX5 p.Arg593Pro Uncertain significance ★ ⚠ same residue
- PEX5 p.Arg593Gln 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-arg593 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown