Is E2F8 p.Thr632= (c.1896C>T) pathogenic?

E2F8 p.Thr632= (c.1896C>T) is classified Benign in E2F8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-08). Common (popmax 5.25%, afr) — too common for a highly-penetrant pathogenic allele.

E2F8 p.Thr632=

Q: How common is E2F8 p.Thr632= (c.1896C>T) in the general population?

E2F8 p.Thr632= (c.1896C>T) is common (popmax 5.25%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1896C>T · rs796969 · VCV789793

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.25%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1	GERP 3.3, phastCons 1
Overall
CADD	8.908	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.25% African / African-American · 3,935/74,886 alleles

Filtering AF 5.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.06%

Overall 0.279% 4,491/1,612,220 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.25%	19
Remaining individualsnot grpmax-eligible	0.343%	292
Admixed American	0.314%	319
Middle Eastern	0.215%	466
European (non-Finnish)	0.0117%	8,547
South Asian	0.0055%	18,171

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.Thr632=
Coding: c.1896C>T
dbSNP: rs796969
Type: single nucleotide variant
Location: chr11:19225862 (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-thr632 (accessed [today's date]).

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