PEX6 p.Lys976=
c.2928G>A · rs1230978438 · VCV753630
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.129%, eas)
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 3.2 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 12.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.129%
East Asian · 58/44,886 alleles
Filtering AF
0.103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.093%
Overall
0.00384%
62/1,613,684 alleles · rare
exomes 58/1,461,430 · genomes 4/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.129% | 774 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,239 |
| European (non-Finnish) | 0.000169% | 590,005 |
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.Lys976=
- Coding
- c.2928G>A
- MANE Select
- NM_000287
- dbSNP
- rs1230978438
- Type
- single nucleotide variant
- Location
- chr6:42964350 (GRCh38)
- Gene constraint
- LOEUF 0.799 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.87
Similar variants
- 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
- PEX6 c.2095-2A>G 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-lys976 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown