PEX5 p.Ser600=
c.1800G>A · rs370306007 · VCV728603
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Conditions
2
peroxisome biogenesis disorder 2A (Zellweger)
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 -3.7 | GERP -3.3 |
| Overall | ||
| CADD | 3.069 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00615%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00573%
Overall
0.0062%
100/1,614,094 alleles · ultra-rare
exomes 92/1,461,890 · genomes 8/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| European (non-Finnish) | 0.00746% | 13,410 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| African / African-American | 0.004% | 24,978 |
| South Asian | 0.00329% | 30,362 |
| East Asian | 0.00223% | 44,896 |
| Admixed American | 0.00167% | 60,008 |
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.Ser600=
- Coding
- c.1800G>A
- MANE Select
- NM_001351132
- dbSNP
- rs370306007
- Type
- single nucleotide variant
- Location
- chr12:7210103 (GRCh38)
- Gene constraint
- LOEUF 0.768 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.28 · 11 PDB
- Residue 600
- 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 UniProt-annotated variant site (in pbd2b; infantile refsum disease; mildly affects peroxisomal protein import); an α-helix
Similar variants
- PEX5 p.Ser600Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- PEX5 p.Ser600Trp Likely pathogenic ★ 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
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-ser600 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown