PEX6 p.Glu45=
c.135G>A · rs2150240712 · VCV1138139
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0232%, mid)
Conditions
1
peroxisome biogenesis disorder
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 0.78 | GERP 0.58, phastCons 1 |
| Overall | ||
| CADD | 10.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0232%
Middle Eastern · 1/4,316 alleles
Overall
0.000131%
2/1,521,016 alleles · ultra-rare
exomes 2/1,368,724 · genomes 0/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0232% | 4,316 |
| European (non-Finnish) | 8.76e-05% | 1,141,229 |
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
- PEX6
- Protein
- p.Glu45=
- Coding
- c.135G>A
- MANE Select
- NM_000287
- dbSNP
- rs2150240712
- Type
- single nucleotide variant
- Location
- chr6:42979016 (GRCh38)
- Gene constraint
- LOEUF 0.799 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.87
Similar variants
- PEX6 p.Glu45Ter Likely pathogenic ★ same residue
- PEX6 c.1130+1G>A Likely pathogenic ★★ same condition
- PEX6 c.1233+1G>A Likely pathogenic ★★ same condition
- PEX6 c.1688+1G>A Pathogenic ★★ same condition
- PEX6 c.1689-1G>A Likely pathogenic ★★ same condition
- PEX6 c.1885-1G>A Likely pathogenic ★★ same condition
- PEX6 c.1962-1G>A Pathogenic/Likely pathogenic ★★ same condition
- PEX6 c.2094+1G>A 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/pex6-p-glu45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown