PEX2 p.Ala22Val
c.65C>T · VCV4900932
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4322 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4322 | ambiguous |
|---|---|---|
| REVEL | 0.709 | pathogenic-leaning |
| SaProt | LLR -10.93 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.4, phastCons 1 |
| Regional constraint | o/e 0.99 | unconstrained · MANE · 914 bp · p 0.85 · regional, not allelic |
| Overall | ||
| CADD | 25.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PEX2
- Protein
- p.Ala22Val
- Coding
- c.65C>T
- MANE Select
- NM_000318
- Type
- single nucleotide variant
- Location
- chr8:76984114 (GRCh38)
- Gene constraint
- LOEUF 1.057 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.17
Similar variants
- PEX2 p.Ala22= Likely benign ★ same residue
- PEX2 c.-17-2A>G Pathogenic/Likely pathogenic ★★ same type
- PEX2 p.Arg119Ter Pathogenic ★★ same type
- PEX2 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same type
- PEX2 p.Gln31Ter Pathogenic/Likely pathogenic ★★ same type
- PEX2 p.Gln78Ter Pathogenic/Likely pathogenic ★★ same type
- PEX2 p.Gln96Ter Pathogenic ★★ same type
- PEX2 p.Glu168Ter Pathogenic/Likely pathogenic ★★ same type
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-ala22val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown