Is E2F4 p.Pro15Leu (c.44C>T) pathogenic?

E2F4 p.Pro15Leu (c.44C>T) is classified Uncertain significance in E2F4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). AlphaMissense: likely pathogenic (0.8229); Absent from gnomAD v4.1.

How common is E2F4 p.Pro15Leu (c.44C>T) in the general population?

E2F4 p.Pro15Leu (c.44C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about E2F4 p.Pro15Leu (c.44C>T)?

AlphaMissense predicts likely pathogenic (score 0.8229) — an in-silico prediction, not a clinical call.

E2F4 p.Pro15Leu

c.44C>T · VCV4246124

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8229 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,324,892)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8229	likely pathogenic
REVEL	0.203	benign-leaning
SaProt	LLR -12.12	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 1.30	unconstrained · MANE · 62 bp · p 0.099 · regional, not allelic
Overall
CADD	29.6	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

No allele count reported in gnomAD v4.1 (AN 1,324,892). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: E2F4
Protein: p.Pro15Leu
Coding: c.44C>T
MANE Select: NM_001950
Type: single nucleotide variant
Location: chr16:67192271 (GRCh38)
Gene constraint: LOEUF 0.615 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 65.56 · 2 PDB
Residue 15: the 'disordered' region

Full E2F4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

E2F4 p.Pro15Arg Uncertain significance ★ ⚠ same residue
E2F4 p.Ala138Val Uncertain significance ★ ⚠ same type
E2F4 p.Ala150Thr Uncertain significance ★ ⚠ same type
E2F4 p.Ala239Gly Uncertain significance ★ ⚠ same type
E2F4 p.Ala239Pro Uncertain significance ★ ⚠ same type
E2F4 p.Ala2Gly Uncertain significance ★ ⚠ same type
E2F4 p.Ala340Ser Uncertain significance ★ ⚠ same type
E2F4 p.Ala4Pro Uncertain significance ★ ⚠ 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/e2f4-p-pro15leu (accessed [today's date]).

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