E2F1 p.Thr247=
c.741G>A · rs35807460 · VCV3037820
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.54%, afr)
Conditions
1
E2F1-related disorder
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>A here scores Δ0.27 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP -2.4, phastCons 1 |
| Overall | ||
| CADD | 13.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.54%
African / African-American · 1,152/75,026 alleles
Filtering AF
1.46%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.43%
Overall
0.0905%
1,460/1,613,974 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.54% | 65 |
| Ashkenazi Jewishnot grpmax-eligible | 0.193% | 519 |
| Middle Eastern | 0.132% | 757 |
| Remaining individualsnot grpmax-eligible | 0.131% | 762 |
| Admixed American | 0.105% | 952 |
| European (non-Finnish) | 0.00805% | 12,420 |
| South Asian | 0.00329% | 30,358 |
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
- E2F1
- Protein
- p.Thr247=
- Coding
- c.741G>A
- MANE Select
- NM_005225
- dbSNP
- rs35807460
- Type
- single nucleotide variant
- Location
- chr20:33677525 (GRCh38)
- Gene constraint
- LOEUF 0.399 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 63.40 · 8 PDB
- Residue 247
- a β-strand; the 'required for interaction with trim28' region; the 'dimerization' region
Disease context
E2F1-related disorder
Similar variants
- RBP3 p.Lys247Arg Uncertain significance ★ ⚠ same residue
- RBP3 p.Arg388Ter Pathogenic ★★ same condition
- RBP3 p.Gln141Ter Pathogenic/Likely pathogenic ★★ same condition
- RBP3 p.Glu692Ter Pathogenic/Likely pathogenic ★★ same condition
- RBP3 p.Tyr784Ter Pathogenic/Likely pathogenic ★★ same condition
- RBP3 p.Tyr841Ter Pathogenic/Likely pathogenic ★★ same condition
- RBP3 c.3055-2A>G Likely pathogenic ★ same condition
- RBP3 p.Gln742Ter Likely pathogenic ★ same condition
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/e2f1-p-thr247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown