EIF2B4 p.Ser12=
c.36G>A · rs778090500 · VCV1567838
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0416%, 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 0.74 | GERP 0.66, phastCons 1 |
| Overall | ||
| CADD | 12.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0416%
Admixed American · 23/55,242 alleles
Filtering AF
0.0284%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0241%
Overall
0.00152%
24/1,583,108 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0416% | 2,402 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,280 |
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.Ser12=
- Coding
- c.36G>A
- MANE Select
- NM_001034116
- dbSNP
- rs778090500
- Type
- single nucleotide variant
- Location
- chr2:27369915 (GRCh38)
- Gene constraint
- LOEUF 0.687 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.37 · 38 PDB
- Residue 12
- the 'disordered' region; a modified residue (phosphoserine)
Similar variants
- EIF2B4 p.Ser12Leu Uncertain significance ★ ⚠ same residue
- 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
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-ser12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown