EIF2B4 p.Asp490=
c.1470T>C · rs376099446 · VCV1541743
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0641%, 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 -0.083 | GERP -1.1, phastCons 0.007 |
| Overall | ||
| CADD | 4.869 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0641%
African / African-American · 48/74,938 alleles
Filtering AF
0.0495%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0444%
Overall
0.00359%
58/1,614,116 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0641% | 1,561 |
| Admixed American | 0.0117% | 8,572 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| European (non-Finnish) | 0.000169% | 590,023 |
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.Asp490=
- Coding
- c.1470T>C
- MANE Select
- NM_001034116
- dbSNP
- rs376099446
- Type
- single nucleotide variant
- Location
- chr2:27364502 (GRCh38)
- Gene constraint
- LOEUF 0.687 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.37 · 38 PDB
- Residue 490
- a β-strand
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-asp490 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown