Is E2F7 p.Arg407Ser (c.1219C>A) pathogenic?

E2F7 p.Arg407Ser (c.1219C>A) is classified Uncertain significance in E2F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). AlphaMissense: ambiguous (0.5033); Ultra-rare (popmax 0.0163%, nfe).

How common is E2F7 p.Arg407Ser (c.1219C>A) in the general population?

E2F7 p.Arg407Ser (c.1219C>A) is ultra-rare (popmax 0.0163%, nfe) (gnomAD).

What do computational predictors say about E2F7 p.Arg407Ser (c.1219C>A)?

AlphaMissense predicts ambiguous (score 0.5033) — an in-silico prediction, not a clinical call.

E2F7 p.Arg407Ser

c.1219C>A · rs149832700 · VCV2398231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5033 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0163%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5033	ambiguous
REVEL	0.298	indeterminate
SaProt	LLR -6.94	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,960 bp · p 0.18 · regional, not allelic
Overall
CADD	25.6	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 0.0163% European (non-Finnish) · 192/1,180,020 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0125% 201/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0163%	6,146
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00312%	32,018
Admixed American	0.00167%	60,004
African / African-American	0.00133%	74,916

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.Arg407Ser
Coding: c.1219C>A
MANE Select: NM_203394
dbSNP: rs149832700
Type: single nucleotide variant
Location: chr12:77033947 (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-arg407ser (accessed [today's date]).

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