Is E2F8 p.Ala487Val (c.1460C>T) pathogenic?

E2F8 p.Ala487Val (c.1460C>T) is classified Uncertain significance in E2F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-14). AlphaMissense: likely benign (0.0731); Ultra-rare (popmax 0.0101%, nfe).

How common is E2F8 p.Ala487Val (c.1460C>T) in the general population?

E2F8 p.Ala487Val (c.1460C>T) is ultra-rare (popmax 0.0101%, nfe) (gnomAD).

What do computational predictors say about E2F8 p.Ala487Val (c.1460C>T)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

E2F8 p.Ala487Val

c.1460C>T · rs745914893 · VCV2471101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.2	phastCons 0.98
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.012 · regional, not allelic
Overall
CADD	17.31	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 0.0101% European (non-Finnish) · 119/1,180,024 alleles

Filtering AF 0.00859% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00803%

Overall 0.00756% 122/1,614,068 alleles · ultra-rare exomes 112/1,461,766 · genomes 10/152,302 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0101%	9,916
Remaining individualsnot grpmax-eligible	0.0048%	20,833

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.Ala487Val
Coding: c.1460C>T
MANE Select: NM_024680
dbSNP: rs745914893
Type: single nucleotide variant
Location: chr11:19229887 (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-ala487val (accessed [today's date]).

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