EIF2B4 p.Ser339=
c.1017A>G · rs935923177 · VCV1627067
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | acceptor loss, 25 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.56 | GERP -1.4, phastCons 0.08 |
| Overall | ||
| CADD | 4.977 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
African / African-American · 10/74,938 alleles
Filtering AF
0.00723%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0055%
Overall
0.000805%
13/1,614,012 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0133% | 7,494 |
| Admixed American | 0.00167% | 59,984 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| European (non-Finnish) | 8.47e-05% | 1,179,981 |
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.Ser339=
- Coding
- c.1017A>G
- MANE Select
- NM_001034116
- dbSNP
- rs935923177
- Type
- single nucleotide variant
- Location
- chr2:27366933 (GRCh38)
- Gene constraint
- LOEUF 0.687 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.37 · 38 PDB
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-ser339 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown