Is E2F1 p.Ser77Arg (c.231T>G) pathogenic?

E2F1 p.Ser77Arg (c.231T>G) is classified Uncertain significance in E2F1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: ambiguous (0.4482); Absent from gnomAD v4.1.

How common is E2F1 p.Ser77Arg (c.231T>G) in the general population?

E2F1 p.Ser77Arg (c.231T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about E2F1 p.Ser77Arg (c.231T>G)?

AlphaMissense predicts ambiguous (score 0.4482) — an in-silico prediction, not a clinical call.

E2F1 p.Ser77Arg

c.231T>G · rs2515398621 · VCV3086733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4482 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4482	ambiguous
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.65	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.55, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 6,229 bp · p 1.9e-06 · regional, not allelic
Overall
CADD	13.09	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: E2F1
Protein: p.Ser77Arg
Coding: c.231T>G
MANE Select: NM_005225
dbSNP: rs2515398621
Type: single nucleotide variant
Location: chr20:33686034 (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 77: the 'disordered' region; the 'cyclin a:cdk2 binding' region

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

Similar variants

RBP3 p.Gly77Arg Uncertain significance ★★ ⚠ 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-ser77arg (accessed [today's date]).

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