PEX2 p.Arg125=
c.373C>A · rs61752124 · VCV1385776
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Conditions
1
peroxisome biogenesis disorder 5A (Zellweger)
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 5.2 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 9.199 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,072 alleles
Overall
0.000124%
2/1,614,022 alleles · very rare
exomes 2/1,461,828 · genomes 0/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,072 |
| European (non-Finnish) | 8.47e-05% | 1,179,986 |
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.Arg125=
- Coding
- c.373C>A
- MANE Select
- NM_000318
- dbSNP
- rs61752124
- Type
- single nucleotide variant
- Location
- chr8:76983806 (GRCh38)
- Gene constraint
- LOEUF 1.057 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.17
- Residue 125
- a UniProt-annotated variant site (in pbd5a); a UniProt-annotated variant site (in pbd5b and pbd5a)
Similar variants
- PEX2 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same residue
- PEX2 p.Arg125Gln Uncertain significance ★★ ⚠ same residue
- PEX2 p.Arg125Gly Uncertain significance ★ ⚠ same residue
- PEX2 c.-17-2A>G Pathogenic/Likely pathogenic ★★ same condition
- PEX2 p.Arg119Ter 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-arg125 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown