Is E2F3 p.Pro116Leu (c.347C>T) pathogenic?

E2F3 p.Pro116Leu (c.347C>T) is classified Benign in E2F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-09). AlphaMissense: likely benign (0.1126); Low-frequency (popmax 2.08%, afr).

How common is E2F3 p.Pro116Leu (c.347C>T) in the general population?

E2F3 p.Pro116Leu (c.347C>T) is low-frequency (popmax 2.08%, afr) (gnomAD).

What do computational predictors say about E2F3 p.Pro116Leu (c.347C>T)?

AlphaMissense predicts likely benign (score 0.1126) — an in-silico prediction, not a clinical call.

E2F3 p.Pro116Leu

c.347C>T · rs189058327 · VCV708917

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1126 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.08%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1126	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.66	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 3.6	GERP 0.99, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 79 kb · p 0.9 · regional, not allelic
Overall
CADD	19.71	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 2.08% African / African-American · 1,434/68,792 alleles

Filtering AF 1.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.96%

Overall 0.116% 1,744/1,497,894 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.08%	48
Admixed American	0.246%	406
Remaining individualsnot grpmax-eligible	0.17%	590
Middle Eastern	0.122%	823
European (non-Finnish)	0.00888%	11,259
South Asian	0.00878%	11,384

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: E2F3
Protein: p.Pro116Leu
Coding: c.347C>T
MANE Select: NM_001949
dbSNP: rs189058327
Type: single nucleotide variant
Location: chr6:20402579 (GRCh38)
Gene constraint: LOEUF 0.393 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.16
Residue 116: the 'disordered' region; the 'cyclin a/cdk2 binding' region

Full E2F3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

E2F3 p.Asp389Asn Benign ★★ same type
E2F3 p.Ala404Ser Uncertain significance ★ ⚠ same type
E2F3 p.Ala450Gly Uncertain significance ★ ⚠ same type
E2F3 p.Ala8Ser Uncertain significance ★ ⚠ same type
E2F3 p.Arg121Cys Uncertain significance ★ ⚠ same type
E2F3 p.Arg305Gln Uncertain significance ★ ⚠ same type
E2F3 p.Asn369Asp Uncertain significance ★ ⚠ same type
E2F3 p.Asn396His 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/e2f3-p-pro116leu (accessed [today's date]).

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