PEX12 p.Asp289=
c.867C>T · rs138720627 · VCV768872
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.99%, afr)
Conditions
2
peroxisome biogenesis disorder type 3B
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 | phastCons 1 |
| Overall | ||
| CADD | 7.086 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.99%
African / African-American · 1,494/75,028 alleles
Filtering AF
1.91%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.87%
Overall
0.11%
1,781/1,614,172 alleles · low-frequency
exomes 879/1,461,862 · genomes 902/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.99% | 50 |
| Remaining individualsnot grpmax-eligible | 0.154% | 651 |
| Admixed American | 0.152% | 660 |
| Middle Eastern | 0.0495% | 2,020 |
| European (non-Finnish) | 0.00797% | 12,553 |
| South Asian | 0.00329% | 30,361 |
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.Asp289=
- Coding
- c.867C>T
- MANE Select
- NM_000286
- dbSNP
- rs138720627
- Type
- single nucleotide variant
- Location
- chr17:35575995 (GRCh38)
- Gene constraint
- LOEUF 1.218 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.58
- Residue 289
- a UniProt-annotated variant site (in pbd3a)
Similar variants
- PEX12 p.Asp289_Tyr290del Uncertain significance ★ same residue
- 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
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-asp289 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown