PEX5 p.Ala625=
c.1875G>A · rs371233272 · VCV310434
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00934%, afr)
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 -0.31 | GERP -3.6, phastCons 0.21 |
| Overall | ||
| CADD | 6.434 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00934%
African / African-American · 7/74,938 alleles
Filtering AF
0.00631%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00584%
Overall
0.00669%
108/1,614,102 alleles · very rare
exomes 94/1,461,878 · genomes 14/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00934% | 10,705 |
| European (non-Finnish) | 0.00763% | 13,112 |
| South Asian | 0.00549% | 18,219 |
| Finnishnot grpmax-eligible | 0.00469% | 21,343 |
| East Asian | 0.00223% | 44,890 |
| Admixed American | 0.00167% | 60,008 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
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.Ala625=
- Coding
- c.1875G>A
- MANE Select
- NM_001351132
- dbSNP
- rs371233272
- Type
- single nucleotide variant
- Location
- chr12:7210178 (GRCh38)
- Gene constraint
- LOEUF 0.768 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.28 · 11 PDB
- Residue 625
- 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)
Similar variants
- PEX5 p.Ala625Thr Uncertain significance ★★ ⚠ same residue
- PEX5 p.Ala625Val Uncertain significance ★★ ⚠ same residue
- PEX5 p.Ala625Glu 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-ala625 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown