Is E2F5 p.Asp324Asn (c.970G>A) pathogenic?

E2F5 p.Asp324Asn (c.970G>A) is classified Uncertain significance in E2F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely pathogenic (0.8347); Ultra-rare (popmax 0.015%, amr).

How common is E2F5 p.Asp324Asn (c.970G>A) in the general population?

E2F5 p.Asp324Asn (c.970G>A) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about E2F5 p.Asp324Asn (c.970G>A)?

AlphaMissense predicts likely pathogenic (score 0.8347) — an in-silico prediction, not a clinical call.

E2F5 p.Asp324Asn

c.970G>A · VCV3843184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8347 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8347	likely pathogenic
REVEL	0.702	pathogenic-leaning
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 36 kb · p 0.039 · regional, not allelic
Overall
CADD	29.2	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 0.015% Admixed American · 9/59,946 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.000558% 9/1,613,212 alleles · ultra-rare

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: E2F5
Protein: p.Asp324Asn
Coding: c.970G>A
MANE Select: NM_001951
Type: single nucleotide variant
Location: chr8:85213791 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.06 · 1 PDB
Residue 324: the 'transactivation' region; the 'rbl2 association' region

Full E2F5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

E2F5 p.Ala192Ser Uncertain significance ★ ⚠ same type
E2F5 p.Ala295Glu Uncertain significance ★ ⚠ same type
E2F5 p.Ala44Thr Uncertain significance ★ ⚠ same type
E2F5 p.Ala44Val Uncertain significance ★ ⚠ same type
E2F5 p.Ala78Glu Uncertain significance ★ ⚠ same type
E2F5 p.Asn183Lys Uncertain significance ★ ⚠ same type
E2F5 p.Asp163Gly Uncertain significance ★ ⚠ same type
E2F5 p.Asp177Glu Uncertain significance ★ ⚠ same type

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/e2f5-p-asp324asn (accessed [today's date]).

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