Is E2F7 p.Ser723Phe (c.2168C>T) pathogenic?

E2F7 p.Ser723Phe (c.2168C>T) is classified Uncertain significance in E2F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.1896); Absent from gnomAD v4.1.

How common is E2F7 p.Ser723Phe (c.2168C>T) in the general population?

E2F7 p.Ser723Phe (c.2168C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about E2F7 p.Ser723Phe (c.2168C>T)?

AlphaMissense predicts likely benign (score 0.1896) — an in-silico prediction, not a clinical call.

E2F7 p.Ser723Phe

c.2168C>T · rs2499020578 · VCV2484569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1896 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1896	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -9.77	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 9.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,960 bp · p 0.18 · regional, not allelic
Overall
CADD	23.0	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

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: E2F7
Protein: p.Ser723Phe
Coding: c.2168C>T
MANE Select: NM_203394
dbSNP: rs2499020578
Type: single nucleotide variant
Location: chr12:77025955 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 51.31

Full E2F7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

E2F7 p.Arg645Thr Benign ★★ same type
E2F7 p.Asp478= Benign ★★ same type
E2F7 p.Pro431= Benign ★★ same type
E2F7 p.Pro857= Benign ★★ same type
E2F7 p.Tyr843= Benign ★★ same type
E2F7 p.Ala117Thr Uncertain significance ★ ⚠ same type
E2F7 p.Ala131Thr Uncertain significance ★ ⚠ same type
E2F7 p.Ala406Ser 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/e2f7-p-ser723phe (accessed [today's date]).

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