EIF2B3 p.Arg15=
c.45G>A · rs539080262 · VCV744270
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0417%, 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 -0.015 | GERP -0.33, phastCons 0.77 |
| Overall | ||
| CADD | 9.465 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0417%
South Asian · 38/91,034 alleles
Filtering AF
0.0312%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0276%
Overall
0.00862%
139/1,612,804 alleles · ultra-rare
exomes 130/1,461,878 · genomes 9/150,926 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0417% | 2,396 |
| African / African-American | 0.0107% | 9,326 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,413 |
| European (non-Finnish) | 0.0072% | 13,881 |
| Admixed American | 0.00168% | 59,618 |
| Finnishnot grpmax-eligible | 0.00157% | 63,816 |
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.Arg15=
- Coding
- c.45G>A
- MANE Select
- NM_020365
- dbSNP
- rs539080262
- Type
- single nucleotide variant
- Location
- chr1:44981124 (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.Arg15Gln Uncertain significance ★★ ⚠ same residue
- EIF2B3 p.Arg15Trp 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-arg15 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown