Is E2F1 p.Pro58Ser (c.172C>T) pathogenic?

E2F1 p.Pro58Ser (c.172C>T) is classified Uncertain significance in E2F1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). AlphaMissense: likely benign (0.0696); Very rare (popmax 0.0084%, afr).

How common is E2F1 p.Pro58Ser (c.172C>T) in the general population?

E2F1 p.Pro58Ser (c.172C>T) is very rare (popmax 0.0084%, afr) (gnomAD).

What do computational predictors say about E2F1 p.Pro58Ser (c.172C>T)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

E2F1 p.Pro58Ser

c.172C>T · VCV4015803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0084%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -6.68	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 2.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 189 bp · p 0.47 · regional, not allelic
Overall
CADD	14.26	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 0.0084% African / African-American · 5/59,492 alleles

Filtering AF 0.00325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.000824% 9/1,091,778 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0084%	11,898
European (non-Finnish)	0.000444%	225,128

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.Pro58Ser
Coding: c.172C>T
MANE Select: NM_005225
Type: single nucleotide variant
Location: chr20:33686093 (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 58: the 'disordered' region

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

Similar variants

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RBP3 p.Glu692Ter Pathogenic/Likely pathogenic ★★ same type
RBP3 p.Tyr784Ter Pathogenic/Likely pathogenic ★★ same type
RBP3 p.Tyr841Ter Pathogenic/Likely pathogenic ★★ same type
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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-pro58ser (accessed [today's date]).

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