PEX12 p.Phe63=
c.189T>C · rs369640430 · VCV765820
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0107%, afr)
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.7 | phastCons 0.66 |
| Overall | ||
| CADD | 7.141 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0107%
African / African-American · 8/74,930 alleles
Filtering AF
0.00528%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.00359%
58/1,613,696 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0107% | 9,366 |
| European (non-Finnish) | 0.00415% | 24,082 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
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.Phe63=
- Coding
- c.189T>C
- MANE Select
- NM_000286
- dbSNP
- rs369640430
- Type
- single nucleotide variant
- Location
- chr17:35577529 (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-phe63 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown