Is E2F7 p.Glu604Lys (c.1810G>A) pathogenic?

E2F7 p.Glu604Lys (c.1810G>A) is classified Uncertain significance in E2F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.0695); Ultra-rare (popmax 0.0143%, sas).

How common is E2F7 p.Glu604Lys (c.1810G>A) in the general population?

E2F7 p.Glu604Lys (c.1810G>A) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

What do computational predictors say about E2F7 p.Glu604Lys (c.1810G>A)?

AlphaMissense predicts likely benign (score 0.0695) — an in-silico prediction, not a clinical call.

E2F7 p.Glu604Lys

c.1810G>A · rs370240683 · VCV2537713

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0695 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0695	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -8.12	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 0.095	GERP -0.094
Regional constraint	o/e 0.95	unconstrained · MANE · 9,960 bp · p 0.18 · regional, not allelic
Overall
CADD	8.231	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

Grpmax group 0.0143% South Asian · 13/91,086 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.00124% 20/1,614,260 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	7,007
East Asian	0.00891%	11,223
Remaining individualsnot grpmax-eligible	0.0048%	20,837

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.Glu604Lys
Coding: c.1810G>A
MANE Select: NM_203394
dbSNP: rs370240683
Type: single nucleotide variant
Location: chr12:77029905 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 51.31
Residue 604: the 'disordered' region

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-glu604lys (accessed [today's date]).

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