Is E2F8 p.Ser68= (c.204T>C) pathogenic?

E2F8 p.Ser68= (c.204T>C) is classified Benign in E2F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-23). Low-frequency (popmax 1.46%, afr).

How common is E2F8 p.Ser68= (c.204T>C) in the general population?

E2F8 p.Ser68= (c.204T>C) is low-frequency (popmax 1.46%, afr) (gnomAD).

E2F8 p.Ser68=

c.204T>C · rs12291291 · VCV786190

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.46%, afr)

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 0.27	phastCons 0.27
Overall
CADD	9.002	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.46% African / African-American · 1,097/74,994 alleles

Filtering AF 1.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.36%

Overall 0.0789% 1,274/1,614,068 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.46%	68
Admixed American	0.108%	923
Remaining individualsnot grpmax-eligible	0.104%	962
Middle Eastern	0.099%	1,010
South Asian	0.00329%	30,360
European (non-Finnish)	0.00322%	31,053

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.Ser68=
Coding: c.204T>C
dbSNP: rs12291291
Type: single nucleotide variant
Location: chr11:19237944 (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-ser68 (accessed [today's date]).

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