Is PEX5 p.Asn520= (c.1560T>C) pathogenic?

PEX5 p.Asn520= (c.1560T>C) is classified Conflicting classifications of pathogenicity in PEX5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-26). Ultra-rare (popmax 0.0339%, mid); Associated with peroxisome biogenesis disorder 2B.

What condition is associated with PEX5 p.Asn520= (c.1560T>C)?

PEX5 p.Asn520= (c.1560T>C) is associated with peroxisome biogenesis disorder 2B (ClinVar).

How common is PEX5 p.Asn520= (c.1560T>C) in the general population?

PEX5 p.Asn520= (c.1560T>C) is ultra-rare (popmax 0.0339%, mid) (gnomAD).

PEX5 p.Asn520=

c.1560T>C · rs140330381 · VCV1401445

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0339%, mid)

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 -0.18	GERP -3.7, phastCons 0.68
Overall
CADD	10.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0339% Middle Eastern · 2/5,896 alleles

Filtering AF 0.00597% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00248%

Overall 0.00297% 48/1,613,514 alleles · ultra-rare exomes 47/1,461,528 · genomes 1/151,986 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0339%	2,948
Remaining individualsnot grpmax-eligible	0.00641%	15,609
European (non-Finnish)	0.00356%	28,093

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.Asn520=
Coding: c.1560T>C
MANE Select: NM_001351132
dbSNP: rs140330381
Type: single nucleotide variant
Location: chr12:7209170 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB
Residue 520: 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)

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.Asn520Ser Conflicting classifications of pathogenicity ★ ⚠ 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-asn520 (accessed [today's date]).

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