Is E2F3 p.Ile307Ser (c.920T>G) pathogenic?

E2F3 p.Ile307Ser (c.920T>G) is classified Uncertain significance in E2F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-28). AlphaMissense: likely pathogenic (0.9716); Ultra-rare (popmax 0.0907%, afr).

How common is E2F3 p.Ile307Ser (c.920T>G) in the general population?

E2F3 p.Ile307Ser (c.920T>G) is ultra-rare (popmax 0.0907%, afr) (gnomAD).

What do computational predictors say about E2F3 p.Ile307Ser (c.920T>G)?

AlphaMissense predicts likely pathogenic (score 0.9716) — an in-silico prediction, not a clinical call.

E2F3 p.Ile307Ser

c.920T>G · rs192596458 · VCV3086741

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9716 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0907%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9716	likely pathogenic
REVEL	0.632	indeterminate
SaProt	LLR -12.43	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.82, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 7,665 bp · p 0.01 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.0907% African / African-American · 68/74,952 alleles

Filtering AF 0.0734% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0671%

Overall 0.00515% 83/1,612,344 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0907%	1,102
Middle Eastern	0.0165%	6,050
Admixed American	0.0101%	9,917
Remaining individualsnot grpmax-eligible	0.00961%	10,407
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,554
South Asian	0.0011%	90,708

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.Ile307Ser
Coding: c.920T>G
MANE Select: NM_001949
dbSNP: rs192596458
Type: single nucleotide variant
Location: chr6:20486724 (GRCh38)
Gene constraint: LOEUF 0.393 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.16
Residue 307: the 'dimerization' 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-ile307ser (accessed [today's date]).

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