Is E2F1 p.Asp381Asn (c.1141G>A) pathogenic?

E2F1 p.Asp381Asn (c.1141G>A) is classified Uncertain significance in E2F1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-19). AlphaMissense: likely benign (0.2123); Very rare (popmax 0.00136%, afr).

How common is E2F1 p.Asp381Asn (c.1141G>A) in the general population?

E2F1 p.Asp381Asn (c.1141G>A) is very rare (popmax 0.00136%, afr) (gnomAD).

What do computational predictors say about E2F1 p.Asp381Asn (c.1141G>A)?

AlphaMissense predicts likely benign (score 0.2123) — an in-silico prediction, not a clinical call.

E2F1 p.Asp381Asn

c.1141G>A · rs1453160857 · VCV2538634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2123	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -7.83	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 7.7	GERP 6.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 533 bp · p 0.17 · regional, not allelic
Overall
CADD	23.8	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

Grpmax group 0.00136% African / African-American · 1/73,798 alleles

Filtering AF 0.000252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000162%

Overall 0.000574% 9/1,568,752 alleles · very rare exomes 8/1,416,532 · genomes 1/152,220 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00136%	73,798
South Asian	0.00116%	86,194
European (non-Finnish)	0.000605%	165,162

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: E2F1
Protein: p.Asp381Asn
Coding: c.1141G>A
MANE Select: NM_005225
dbSNP: rs1453160857
Type: single nucleotide variant
Location: chr20:33676905 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 381: the 'transactivation' region; the 'required for interaction with trim28' region

Full E2F1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RBP3 p.Glu381Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
RBP3 p.Arg388Ter Pathogenic ★★ same type
RBP3 p.Gln141Ter Pathogenic/Likely pathogenic ★★ same type
RBP3 p.Gln54Ter Pathogenic ★★ same type
RBP3 p.Glu149Ter Pathogenic ★★ same type
RBP3 p.Glu692Ter Pathogenic/Likely pathogenic ★★ same type
RBP3 p.Tyr784Ter Pathogenic/Likely pathogenic ★★ same type
RBP3 p.Tyr841Ter Pathogenic/Likely pathogenic ★★ 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/e2f1-p-asp381asn (accessed [today's date]).

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