Is E2F7 p.Arg645Thr (c.1934G>C) pathogenic?

E2F7 p.Arg645Thr (c.1934G>C) is classified Benign in E2F7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-12). AlphaMissense: likely benign (0.0655); Low-frequency (popmax 2.06%, afr).

How common is E2F7 p.Arg645Thr (c.1934G>C) in the general population?

E2F7 p.Arg645Thr (c.1934G>C) is low-frequency (popmax 2.06%, afr) (gnomAD).

What do computational predictors say about E2F7 p.Arg645Thr (c.1934G>C)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

E2F7 p.Arg645Thr

c.1934G>C · rs36110778 · VCV784305

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.06%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -6.04	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 0.028	GERP -4.1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,960 bp · p 0.18 · regional, not allelic
Overall
CADD	0.608	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 2.06% African / African-American · 1,542/75,020 alleles

Filtering AF 1.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.94%

Overall 0.162% 2,618/1,614,140 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.06%	49
Middle Eastern	0.66%	152
Ashkenazi Jewishnot grpmax-eligible	0.567%	176
Admixed American	0.297%	337
Remaining individualsnot grpmax-eligible	0.274%	366
European (non-Finnish)	0.0431%	2,318
Finnishnot grpmax-eligible	0.0109%	9,147
South Asian	0.00329%	30,357

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.Arg645Thr
Coding: c.1934G>C
MANE Select: NM_203394
dbSNP: rs36110778
Type: single nucleotide variant
Location: chr12:77028089 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 51.31
Residue 645: the 'disordered' region

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

Similar variants

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
E2F7 p.Ala466Val 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-arg645thr (accessed [today's date]).

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