PEX12 p.Phe86=
c.258T>C · rs529434949 · VCV2139682
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
Conditions
1
peroxisome biogenesis disorder 3A (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 0.62 | phastCons 0.92 |
| Overall | ||
| CADD | 8.125 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,888 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.000372%
6/1,614,176 alleles · ultra-rare
exomes 5/1,461,848 · genomes 1/152,328 · joint denominator
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
- PEX12
- Protein
- p.Phe86=
- Coding
- c.258T>C
- MANE Select
- NM_000286
- dbSNP
- rs529434949
- Type
- single nucleotide variant
- Location
- chr17:35577460 (GRCh38)
- Gene constraint
- LOEUF 1.218 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.58
Similar variants
- PEX12 c.126+1G>T Pathogenic/Likely pathogenic ★★ same condition
- PEX12 c.680+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PEX12 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same condition
- PEX12 p.Arg180Ter Pathogenic ★★ same condition
- PEX12 p.Arg202Ter Pathogenic/Likely pathogenic ★★ same condition
- PEX12 p.Gln111Ter Pathogenic/Likely pathogenic ★★ same condition
- PEX12 p.Gln112Ter Pathogenic/Likely pathogenic ★★ same condition
- PEX12 p.Gln209Ter 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/pex12-p-phe86 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown