Is E2F2 p.Pro79Gln (c.236C>A) pathogenic?

E2F2 p.Pro79Gln (c.236C>A) is classified Uncertain significance in E2F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.1301); Absent from gnomAD v4.1.

How common is E2F2 p.Pro79Gln (c.236C>A) in the general population?

E2F2 p.Pro79Gln (c.236C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about E2F2 p.Pro79Gln (c.236C>A)?

AlphaMissense predicts likely benign (score 0.1301) — an in-silico prediction, not a clinical call.

E2F2 p.Pro79Gln

c.236C>A · VCV4015810

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1301 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1301	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 0.81, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 21 kb · p 0.0011 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: E2F2
Protein: p.Pro79Gln
Coding: c.236C>A
MANE Select: NM_004091
Type: single nucleotide variant
Location: chr1:23530558 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.42 · 1 PDB
Residue 79: the 'cyclin a/cdk2 binding' region

Full E2F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

E2F2 p.Pro79Arg Uncertain significance ★ ⚠ same residue
E2F2 p.Pro79Leu Uncertain significance ★ ⚠ same residue
E2F2 p.Pro310Leu Benign ★★ same type
E2F2 p.Thr202Ile Likely benign ★★ ⚠ same type
E2F2 p.Ala158Thr Uncertain significance ★ ⚠ same type
E2F2 p.Ala21Val Uncertain significance ★ ⚠ same type
E2F2 p.Ala223Val Uncertain significance ★ ⚠ same type
E2F2 p.Ala395Val 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/e2f2-p-pro79gln (accessed [today's date]).

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