E2F1 p.Phe399Leu
c.1197C>G · VCV4246099
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9544 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9544 | likely pathogenic |
|---|---|---|
| REVEL | 0.186 | benign-leaning |
| SaProt | LLR -5.40 | tolerated |
| ⇒ AlphaMissense calls this damaging; REVEL and SaProt do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 5.2, phastCons 1 |
| Regional constraint | o/e 0.90 | unconstrained · MANE · 533 bp · p 0.17 · regional, not allelic |
| Overall | ||
| CADD | 24.7 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- E2F1
- Protein
- p.Phe399Leu
- Coding
- c.1197C>G
- MANE Select
- NM_005225
- Type
- single nucleotide variant
- Location
- chr20:33676849 (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 399
- the 'transactivation' region
Similar variants
- RBP3 p.Pro399= Likely benign ★★ 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-phe399leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown