EIF2B2 p.Ile336=
c.1008C>T · rs140707986 · VCV731462
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.225%, 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 1.4 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 10.41 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.225%
African / African-American · 169/75,020 alleles
Filtering AF
0.197%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.187%
Overall
0.012%
193/1,614,122 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.225% | 444 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
| Admixed American | 0.0117% | 8,574 |
| South Asian | 0.0011% | 91,078 |
| European (non-Finnish) | 0.000678% | 147,501 |
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
- EIF2B2
- Protein
- p.Ile336=
- Coding
- c.1008C>T
- MANE Select
- NM_014239
- dbSNP
- rs140707986
- Type
- single nucleotide variant
- Location
- chr14:75009140 (GRCh38)
- Gene constraint
- LOEUF 1.25 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.82 · 38 PDB
- Residue 336
- an α-helix
Similar variants
- EIF2B2 c.285-1G>A Likely pathogenic ★★ same type
- EIF2B2 c.832-2A>G Likely pathogenic ★★ same type
- EIF2B2 p.Arg172Ter Pathogenic/Likely pathogenic ★★ same type
- EIF2B2 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same type
- EIF2B2 p.Glu213Gly Pathogenic ★★ ⚠ same type
- EIF2B2 p.Glu304Ter Pathogenic/Likely pathogenic ★★ same type
- EIF2B2 p.Gly200Val Pathogenic/Likely pathogenic ★★ same type
- EIF2B2 p.Lys273Arg Pathogenic/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/eif2b2-p-ile336 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown