Is E2F3 p.Arg295= (c.885G>A) pathogenic?

E2F3 p.Arg295= (c.885G>A) is classified Likely benign in E2F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). Ultra-rare (popmax 0.024%, nfe).

How common is E2F3 p.Arg295= (c.885G>A) in the general population?

E2F3 p.Arg295= (c.885G>A) is ultra-rare (popmax 0.024%, nfe) (gnomAD).

E2F3 p.Arg295=

c.885G>A · VCV3506273

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 2, phastCons 1
Overall
CADD	16.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% European (non-Finnish) · 268/1,117,932 alleles

Filtering AF 0.0216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0206%

Overall 0.0194% 298/1,539,854 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0301%	3,326
European (non-Finnish)grpmax	0.024%	4,171
Middle Eastern	0.0169%	5,902
Admixed American	0.00523%	19,125
South Asian	0.00456%	21,926
Finnishnot grpmax-eligible	0.00313%	31,904
East Asian	0.00225%	44,512
African / African-American	0.00137%	73,096

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg295=
Coding: c.885G>A
MANE Select: NM_001949
Type: single nucleotide variant
Location: chr6:20486689 (GRCh38)
Gene constraint: LOEUF 0.393 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.16
Residue 295: 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-arg295 (accessed [today's date]).

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