Is E2F8 p.Arg372Gln (c.1115G>A) pathogenic?

E2F8 p.Arg372Gln (c.1115G>A) is classified Likely benign in E2F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely benign (0.06); Very rare (popmax 0.00988%, sas).

How common is E2F8 p.Arg372Gln (c.1115G>A) in the general population?

E2F8 p.Arg372Gln (c.1115G>A) is very rare (popmax 0.00988%, sas) (gnomAD).

What do computational predictors say about E2F8 p.Arg372Gln (c.1115G>A)?

AlphaMissense predicts likely benign (score 0.06) — an in-silico prediction, not a clinical call.

E2F8 p.Arg372Gln

c.1115G>A · rs375962806 · VCV2330137

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.06 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.06	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.1
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.012 · regional, not allelic
Overall
CADD	5.008	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 0.00988% South Asian · 9/91,080 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00248% 40/1,614,036 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,120
Remaining individualsnot grpmax-eligible	0.0064%	15,621
East Asian	0.00446%	22,442
Admixed American	0.00333%	29,994
European (non-Finnish)	0.00195%	51,306

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.Arg372Gln
Coding: c.1115G>A
dbSNP: rs375962806
Type: single nucleotide variant
Location: chr11:19230786 (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-arg372gln (accessed [today's date]).

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