EIF3B p.Phe606=
c.1818C>T · rs748044149 · VCV2657230
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.5 | GERP -3.7 |
| Overall | ||
| CADD | 8.487 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,080 alleles
Filtering AF
0.0136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.00242%
39/1,613,816 alleles · ultra-rare
exomes 38/1,461,722 · genomes 1/152,094 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0493% | 2,027 |
| South Asian | 0.0209% | 4,793 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,412 |
| Finnishnot grpmax-eligible | 0.00156% | 63,982 |
| European (non-Finnish) | 0.000847% | 117,995 |
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
- EIF3B
- Protein
- p.Phe606=
- Coding
- c.1818C>T
- MANE Select
- NM_001037283
- dbSNP
- rs748044149
- Type
- single nucleotide variant
- Location
- chr7:2374535 (GRCh38)
- Gene constraint
- LOEUF 0.107 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.64 · 21 PDB
Similar variants
- EIF3B p.Asn145= Benign ★★ same type
- EIF3B p.Pro24= Likely benign ★★ same type
- EIF3B p.Ser64Pro Benign ★★ same type
- EIF3B c.1357-16C>T Uncertain significance ★ same type
- EIF3B p.Ala123Thr Uncertain significance ★ ⚠ same type
- EIF3B p.Ala135Pro Uncertain significance ★ ⚠ same type
- EIF3B p.Ala136Val Uncertain significance ★ ⚠ same type
- EIF3B p.Ala238Thr 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/eif3b-p-phe606 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown