PEX6 p.Val868=
c.2604G>A · rs761123181 · VCV1097583
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0373%, sas)
Conditions
1
peroxisome biogenesis disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | acceptor loss · deltas |
|---|---|---|
| Pangolin | Δ0.23 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.1 | GERP 1.5, phastCons 0.47 |
| Overall | ||
| CADD | 4.419 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0373%
South Asian · 34/91,086 alleles
Filtering AF
0.0274%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.024%
Overall
0.00217%
35/1,614,110 alleles · ultra-rare
exomes 34/1,461,880 · genomes 1/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0373% | 2,679 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
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.Val868=
- Coding
- c.2604G>A
- MANE Select
- NM_000287
- dbSNP
- rs761123181
- Type
- single nucleotide variant
- Location
- chr6:42965137 (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-val868 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown