EIF4A2 p.Ser2=
c.6T>C · VCV3385091
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
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 4.1 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 19.72 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,996 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.000496%
8/1,614,026 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 9,999 |
| European (non-Finnish) | 0.000169% | 590,016 |
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
- EIF4A2
- Protein
- p.Ser2=
- Coding
- c.6T>C
- MANE Select
- NM_001967
- Type
- single nucleotide variant
- Location
- chr3:186783616 (GRCh38)
- Gene constraint
- LOEUF 0.298 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.94 · 1 PDB
- Residue 2
- the 'disordered' region; a UniProt-annotated variant site (in nedhss; uncertain significance)
Similar variants
- EIF4A2 p.Ser2Phe Uncertain significance ★ ⚠ same residue
- EIF4A2 p.Ser2Cys Likely pathogenic ⚠ same residue
- EIF4A2 p.Gly362Ser Pathogenic ★★ same type
- EIF4A2 p.Ile278Thr Uncertain significance ★★ ⚠ same type
- EIF4A2 c.517+1G>T Likely pathogenic ★ same type
- EIF4A2 p.Asp338Tyr Likely pathogenic ★ same type
- EIF4A2 p.Gly161Arg Likely pathogenic ★ same type
- EIF4A2 p.Gly161Trp 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/eif4a2-p-ser2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown