EIF2B5 p.Ala645=
c.1935G>A · rs772251891 · VCV1135725
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00667%, afr)
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 -1.2 | GERP -3.7 |
| Overall | ||
| CADD | 6.313 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
African / African-American · 5/74,934 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00164%
Overall
0.00235%
38/1,614,104 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00667% | 14,987 |
| European (non-Finnish) | 0.00263% | 38,066 |
| South Asian | 0.0022% | 45,547 |
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.Ala645=
- Coding
- c.1935G>A
- MANE Select
- NM_003907
- dbSNP
- rs772251891
- Type
- single nucleotide variant
- Location
- chr3:184144164 (GRCh38)
- Gene constraint
- LOEUF 0.544 · pLI 0.16 (gnomAD)
- Structure
- AlphaFold pLDDT 79.35 · 37 PDB
- Residue 645
- an α-helix; the w2 domain
Similar variants
- EIF2B5 p.Ala645Val Likely benign ★★ 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-ala645 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown