PEX2 p.Tyr265=
c.795T>C · rs764785488 · VCV290944
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.03%, amr)
Conditions
2
peroxisome biogenesis disorder 5A (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 -2.7 | GERP -4.9 |
| Overall | ||
| CADD | 0.056 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.03%
Admixed American · 18/60,008 alleles
Filtering AF
0.0194%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.016%
Overall
0.00173%
28/1,614,012 alleles · ultra-rare
exomes 25/1,461,784 · genomes 3/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.03% | 3,334 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| European (non-Finnish) | 0.000763% | 131,114 |
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
- PEX2
- Protein
- p.Tyr265=
- Coding
- c.795T>C
- MANE Select
- NM_000318
- dbSNP
- rs764785488
- Type
- single nucleotide variant
- Location
- chr8:76983384 (GRCh38)
- Gene constraint
- LOEUF 1.057 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.17
- Residue 265
- a UniProt-annotated variant site (in pbd5a); a UniProt-annotated variant site (in pbd5b and pbd5a); a UniProt-annotated variant site (in pbd5b)
Similar variants
- PEX2 p.Tyr265Cys Uncertain significance ★ ⚠ same residue
- PEX2 p.Tyr265fs Uncertain significance ★ same residue
- PEX2 c.-17-2A>G Pathogenic/Likely pathogenic ★★ same condition
- PEX2 p.Arg119Ter Pathogenic ★★ same condition
- PEX2 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same condition
- PEX2 p.Gln31Ter Pathogenic/Likely pathogenic ★★ same condition
- PEX2 p.Gln78Ter Pathogenic/Likely pathogenic ★★ same condition
- PEX2 p.Gln96Ter 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/pex2-p-tyr265 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown