E2F1 p.Ala275=
c.825C>T · rs529768589 · VCV741802
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, afr)
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 -3.5 | GERP -8.8 |
| Overall | ||
| CADD | 0.796 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
African / African-American · 13/75,040 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00811%
Overall
0.00155%
25/1,614,118 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0173% | 5,772 |
| East Asian | 0.00668% | 14,963 |
| Admixed American | 0.00167% | 60,022 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| European (non-Finnish) | 0.000593% | 168,568 |
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.Ala275=
- Coding
- c.825C>T
- MANE Select
- NM_005225
- dbSNP
- rs529768589
- Type
- single nucleotide variant
- Location
- chr20:33677441 (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 275
- a β-strand; the 'required for interaction with trim28' region; the 'dimerization' region
Similar variants
- RBP3 p.Asp275His Uncertain significance ★ ⚠ same residue
- RBP3 p.Arg388Ter Pathogenic ★★ same type
- RBP3 p.Gln141Ter Pathogenic/Likely pathogenic ★★ same type
- RBP3 p.Gln54Ter Pathogenic ★★ same type
- RBP3 p.Glu149Ter Pathogenic ★★ same type
- RBP3 p.Glu692Ter Pathogenic/Likely pathogenic ★★ same type
- RBP3 p.Tyr784Ter Pathogenic/Likely pathogenic ★★ same type
- RBP3 p.Tyr841Ter Pathogenic/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/e2f1-p-ala275 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown