PEX5 p.Ala303=
c.909T>C · rs376649488 · VCV310423
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 0.0312%, eas)
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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.5 | GERP -2.9 |
| Overall | ||
| CADD | 4.956 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0312%
East Asian · 14/44,868 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0151%
Overall
0.00118%
19/1,613,966 alleles · ultra-rare
exomes 14/1,461,748 · genomes 5/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0312% | 3,205 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,625 |
| European (non-Finnish) | 8.47e-05% | 1,179,944 |
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.Ala303=
- Coding
- c.909T>C
- MANE Select
- NM_001351132
- dbSNP
- rs376649488
- Type
- single nucleotide variant
- Location
- chr12:7203494 (GRCh38)
- Gene constraint
- LOEUF 0.768 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.28 · 11 PDB
Similar variants
- 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
- PEX5 p.Arg427Ter 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-ala303 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown