Is E2F7 p.Val70Ala (c.209T>C) pathogenic?

E2F7 p.Val70Ala (c.209T>C) is classified Uncertain significance in E2F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). AlphaMissense: ambiguous (0.4029); Very rare (popmax 0.00534%, afr).

How common is E2F7 p.Val70Ala (c.209T>C) in the general population?

E2F7 p.Val70Ala (c.209T>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about E2F7 p.Val70Ala (c.209T>C)?

AlphaMissense predicts ambiguous (score 0.4029) — an in-silico prediction, not a clinical call.

E2F7 p.Val70Ala

c.209T>C · rs1478344377 · VCV2258400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4029 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Computational evidence

Protein change
AlphaMissense	0.4029	ambiguous
REVEL	0.307	indeterminate
SaProt	LLR -7.21	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 22 kb · p 2.4e-07 · regional, not allelic
Overall
CADD	23.6	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

Grpmax group 0.00534% African / African-American · 4/74,930 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,090 alleles · very rare

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: E2F7
Protein: p.Val70Ala
Coding: c.209T>C
MANE Select: NM_203394
dbSNP: rs1478344377
Type: single nucleotide variant
Location: chr12:77056015 (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-val70ala (accessed [today's date]).

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