Is E2F1 p.Leu415= (c.1245C>T) pathogenic?

E2F1 p.Leu415= (c.1245C>T) is classified Likely benign in E2F1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-10). Rare (popmax 0.281%, mid); Associated with E2F1-related disorder.

What condition is associated with E2F1 p.Leu415= (c.1245C>T)?

E2F1 p.Leu415= (c.1245C>T) is associated with E2F1-related disorder (ClinVar).

How common is E2F1 p.Leu415= (c.1245C>T) in the general population?

E2F1 p.Leu415= (c.1245C>T) is rare (popmax 0.281%, mid) (gnomAD).

E2F1 p.Leu415=

c.1245C>T · rs147013405 · VCV3050503

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.281%, mid)

Conditions

E2F1-related disorder

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 -1.6	GERP -11
Overall
CADD	2.929	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.281% Middle Eastern · 17/6,046 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.046% 738/1,603,292 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.281%	356
Admixed American	0.138%	727
European (non-Finnish)	0.0475%	2,105
Remaining individualsnot grpmax-eligible	0.0451%	2,217
South Asian	0.037%	2,706
African / African-American	0.0254%	3,933
Finnishnot grpmax-eligible	0.00317%	31,589

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.Leu415=
Coding: c.1245C>T
MANE Select: NM_005225
dbSNP: rs147013405
Type: single nucleotide variant
Location: chr20:33676801 (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 415: the 'transactivation' region; the 'rb1 binding' region

Full E2F1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

E2F1-related disorder

Similar variants

RBP3 p.Leu415= 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-leu415 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown