Is E2F1 p.Phe413= (c.1239C>T) pathogenic?

E2F1 p.Phe413= (c.1239C>T) is classified Likely benign in E2F1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). Ultra-rare (popmax 0.0684%, sas); Associated with E2F1-related disorder.

What condition is associated with E2F1 p.Phe413= (c.1239C>T)?

E2F1 p.Phe413= (c.1239C>T) is associated with E2F1-related disorder (ClinVar).

How common is E2F1 p.Phe413= (c.1239C>T) in the general population?

E2F1 p.Phe413= (c.1239C>T) is ultra-rare (popmax 0.0684%, sas) (gnomAD).

E2F1 p.Phe413=

c.1239C>T · rs535111025 · VCV3043057

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0684%, sas)

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 -2.6, phastCons 1
Overall
CADD	8.965	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0684% South Asian · 61/89,142 alleles

Filtering AF 0.0546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0496%

Overall 0.00474% 76/1,602,412 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0684%	1,461
Middle Eastern	0.0165%	6,044
Remaining individualsnot grpmax-eligible	0.00322%	31,009
East Asian	0.00227%	44,124
African / African-American	0.00134%	74,732
European (non-Finnish)	0.000852%	117,420

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.Phe413=
Coding: c.1239C>T
MANE Select: NM_005225
dbSNP: rs535111025
Type: single nucleotide variant
Location: chr20:33676807 (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 413: 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.Pro413Ser 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-phe413 (accessed [today's date]).

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