Is E2F8 p.Ile284Arg (c.851T>G) pathogenic?

E2F8 p.Ile284Arg (c.851T>G) is classified Uncertain significance in E2F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-17). AlphaMissense: likely pathogenic (0.6856); Very rare (popmax 0.00133%, afr).

How common is E2F8 p.Ile284Arg (c.851T>G) in the general population?

E2F8 p.Ile284Arg (c.851T>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about E2F8 p.Ile284Arg (c.851T>G)?

AlphaMissense predicts likely pathogenic (score 0.6856) — an in-silico prediction, not a clinical call.

E2F8 p.Ile284Arg

c.851T>G · VCV3843201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6856	likely pathogenic
REVEL	0.345	indeterminate
SaProt	LLR -11.20	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.2	phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.012 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00133% African / African-American · 1/75,070 alleles

Overall 0.000205% 3/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,070
South Asian	0.0011%	91,084
European (non-Finnish)	8.47e-05%	1,180,045

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.Ile284Arg
Coding: c.851T>G
Type: single nucleotide variant
Location: chr11:19234437 (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-ile284arg (accessed [today's date]).

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