EIF2B5 p.Ala45=
c.135A>G · rs753295628 · VCV1160507
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00529%, amr)
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 -2.4 | GERP -3.3 |
| Overall | ||
| CADD | 9.715 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00529%
Admixed American · 3/56,680 alleles
Filtering AF
0.0014%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000689%
Overall
0.0012%
19/1,589,572 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00529% | 18,893 |
| Remaining individualsnot grpmax-eligible | 0.00325% | 30,734 |
| European (non-Finnish) | 0.0012% | 83,495 |
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
- EIF2B5
- Protein
- p.Ala45=
- Coding
- c.135A>G
- MANE Select
- NM_003907
- dbSNP
- rs753295628
- Type
- single nucleotide variant
- Location
- chr3:184135520 (GRCh38)
- Gene constraint
- LOEUF 0.544 · pLI 0.16 (gnomAD)
- Structure
- AlphaFold pLDDT 79.35 · 37 PDB
- Residue 45
- a β-strand
Similar variants
- EIF2B5 p.Ala45Gly Uncertain significance ★★ ⚠ same residue
- EIF2B5 p.Ala403Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- EIF2B5 p.Arg113Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- EIF2B5 p.Arg113His Pathogenic ★★ ⚠ same type
- EIF2B5 p.Arg121Ter Pathogenic/Likely pathogenic ★★ same type
- EIF2B5 p.Arg136Cys Pathogenic/Likely pathogenic ★★ same type
- EIF2B5 p.Arg136His Pathogenic ★★ same type
- EIF2B5 p.Arg195Cys 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/eif2b5-p-ala45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown