Is E2F2 p.Pro310Leu (c.929C>T) pathogenic?

E2F2 p.Pro310Leu (c.929C>T) is classified Benign in E2F2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-08). AlphaMissense: likely benign (0.0908); Rare (popmax 0.941%, afr).

How common is E2F2 p.Pro310Leu (c.929C>T) in the general population?

E2F2 p.Pro310Leu (c.929C>T) is rare (popmax 0.941%, afr) (gnomAD).

What do computational predictors say about E2F2 p.Pro310Leu (c.929C>T)?

AlphaMissense predicts likely benign (score 0.0908) — an in-silico prediction, not a clinical call.

E2F2 p.Pro310Leu

c.929C>T · rs116576730 · VCV715330

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0908 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.941%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0908	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.45	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 3.4	GERP 0.62, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 21 kb · p 0.0011 · regional, not allelic
Overall
CADD	14.01	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

Grpmax group 0.941% African / African-American · 703/74,734 alleles

Filtering AF 0.883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.86%

Overall 0.0516% 830/1,609,720 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.941%	106
Remaining individualsnot grpmax-eligible	0.0914%	1,094
Admixed American	0.0539%	1,856
Middle Eastern	0.0166%	6,026
South Asian	0.00443%	22,595
European (non-Finnish)	0.00272%	36,815
East Asian	0.00225%	44,428

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: E2F2
Protein: p.Pro310Leu
Coding: c.929C>T
MANE Select: NM_004091
dbSNP: rs116576730
Type: single nucleotide variant
Location: chr1:23516451 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.42 · 1 PDB
Residue 310: the 'disordered' region

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

Similar variants

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
E2F2 p.Ala40Gly Uncertain significance ★ ⚠ same type
E2F2 p.Ala40Val Uncertain significance ★ ⚠ same type
E2F2 p.Ala58Val 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-pro310leu (accessed [today's date]).

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