Is E2F7 p.Trp81Ser (c.242G>C) pathogenic?

E2F7 p.Trp81Ser (c.242G>C) is classified Uncertain significance in E2F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-21). AlphaMissense: likely pathogenic (0.8218); Absent from gnomAD v4.1.

How common is E2F7 p.Trp81Ser (c.242G>C) in the general population?

E2F7 p.Trp81Ser (c.242G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about E2F7 p.Trp81Ser (c.242G>C)?

AlphaMissense predicts likely pathogenic (score 0.8218) — an in-silico prediction, not a clinical call.

E2F7 p.Trp81Ser

c.242G>C · rs2499062595 · VCV3086764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8218 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8218	likely pathogenic
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -2.12	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 22 kb · p 2.4e-07 · regional, not allelic
Overall
CADD	27.6	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: E2F7
Protein: p.Trp81Ser
Coding: c.242G>C
MANE Select: NM_203394
dbSNP: rs2499062595
Type: single nucleotide variant
Location: chr12:77055982 (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-trp81ser (accessed [today's date]).

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