AIMP2 p.Gln45=
c.135G>A · rs2536738764 · VCV2664220
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000436%, nfe)
Conditions
1
leukodystrophy, hypomyelinating, 17
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.57 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.68 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 12 | phastCons 1 |
| Overall | ||
| CADD | 22.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000436%
European (non-Finnish) · 5/1,146,444 alleles
Filtering AF
0.000128%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.3e-05%
Overall
0.000363%
5/1,377,792 alleles · very rare
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
- AIMP2
- Protein
- p.Gln45=
- Coding
- c.135G>A
- MANE Select
- NM_006303
- dbSNP
- rs2536738764
- Type
- single nucleotide variant
- Location
- chr7:6009498 (GRCh38)
- Gene constraint
- LOEUF 1.107 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.65 · 13 PDB
- Residue 45
- a UniProt-annotated variant site (in hld17)
Similar variants
- AIMP2 p.Tyr35Ter Likely pathogenic ★★ same condition
- AIMP2 p.Thr154= Benign/Likely benign ★★ same condition
- AIMP2 p.Val6Leu Benign/Likely benign ★★ same condition
- AIMP2 p.Tyr25Cys Likely pathogenic ★ ⚠ same condition
- AIMP2 p.Met24Arg Uncertain significance ★ ⚠ same condition
- AIMP2 p.Met24fs Pathogenic/Likely pathogenic ★★ same condition
- AIMP2 p.Ser219fs Likely pathogenic ★★ same condition
- PMS2 c.-2146C>A Benign ★★★ 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/aimp2-p-gln45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown