EIF2B3 p.Glu366=
c.1098G>A · rs150426784 · VCV2893908
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00364%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.174 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -0.49, phastCons 1 |
| Overall | ||
| CADD | 8.608 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00364%
European (non-Finnish) · 43/1,180,040 alleles
Filtering AF
0.00275%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00244%
Overall
0.00285%
46/1,614,036 alleles · very rare
exomes 45/1,461,886 · genomes 1/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00364% | 27,443 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| African / African-American | 0.00133% | 74,914 |
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
- EIF2B3
- Protein
- p.Glu366=
- Coding
- c.1098G>A
- MANE Select
- NM_020365
- dbSNP
- rs150426784
- Type
- single nucleotide variant
- Location
- chr1:44874782 (GRCh38)
- Gene constraint
- LOEUF 0.522 · pLI 0.93 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 72.51 · 37 PDB
Similar variants
- EIF2B3 p.Glu366Asp Uncertain significance ★ ⚠ same residue
- EIF2B3 p.Glu366Lys Uncertain significance ★ same residue
- EIF2B3 p.Ala87Val Pathogenic/Likely pathogenic ★★ same type
- EIF2B3 p.Arg225Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- EIF2B3 p.Arg225Trp Likely pathogenic ★★ same type
- EIF2B3 p.Ile346Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- EIF2B3 p.Val30Ala Pathogenic/Likely pathogenic ★★ same type
- EIF2B3 c.784+4A>C 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/eif2b3-p-glu366 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown