Is E2F8 p.Ile674Val (c.2020A>G) pathogenic?

E2F8 p.Ile674Val (c.2020A>G) is classified Benign in E2F8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-08). AlphaMissense: likely benign (0.0644); Common (popmax 5.22%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about E2F8 p.Ile674Val (c.2020A>G)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

E2F8 p.Ile674Val

Q: How common is E2F8 p.Ile674Val (c.2020A>G) in the general population?

E2F8 p.Ile674Val (c.2020A>G) is common (popmax 5.22%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2020A>G · rs793274 · VCV789792

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.22%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -5.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.057	GERP 3, phastCons 0.007
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.012 · regional, not allelic
Overall
CADD	15.6	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 5.22% African / African-American · 3,918/75,030 alleles

Filtering AF 5.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.03%

Overall 0.277% 4,470/1,614,170 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.22%	19
Remaining individualsnot grpmax-eligible	0.315%	317
Admixed American	0.308%	324
Middle Eastern	0.214%	466
European (non-Finnish)	0.0123%	8,138
South Asian	0.0121%	8,280
East Asian	0.00223%	44,882

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: E2F8
Protein: p.Ile674Val
Coding: c.2020A>G
dbSNP: rs793274
Type: single nucleotide variant
Location: chr11:19225738 (GRCh38)

Full E2F8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/e2f8-p-ile674val (accessed [today's date]).

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