EIF2B4 p.Ala5=
c.15C>T · rs575951063 · VCV3018538
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0237%, sas)
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 -0.3 | GERP -3.4, phastCons 0.004 |
| Overall | ||
| CADD | 10.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0237%
South Asian · 20/84,280 alleles
Filtering AF
0.0157%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0131%
Overall
0.00168%
26/1,545,928 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0237% | 4,214 |
| East Asian | 0.00968% | 10,334 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,150 |
| European (non-Finnish) | 8.71e-05% | 1,148,175 |
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
- EIF2B4
- Protein
- p.Ala5=
- Coding
- c.15C>T
- MANE Select
- NM_001034116
- dbSNP
- rs575951063
- Type
- single nucleotide variant
- Location
- chr2:27370300 (GRCh38)
- Gene constraint
- LOEUF 0.687 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.37 · 38 PDB
- Residue 5
- the 'disordered' region
Similar variants
- EIF2B4 c.32-1G>T Likely pathogenic ★★ same type
- EIF2B4 p.Arg357Gln Likely pathogenic ★★ ⚠ same type
- EIF2B4 p.Pro243Leu Pathogenic/Likely pathogenic ★★ same type
- EIF2B4 p.Thr502Met Likely pathogenic ★★ same type
- EIF2B4 p.Tyr489His Pathogenic/Likely pathogenic ★★ same type
- EIF2B4 p.Ala228Thr Uncertain significance ★★ ⚠ same type
- EIF2B4 p.Ala349Thr Uncertain significance ★★ ⚠ same type
- EIF2B4 p.Ala66Thr Uncertain significance ★★ ⚠ 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/eif2b4-p-ala5 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown