Is UBE3A p.Pro847= (c.2541G>A) pathogenic?

UBE3A p.Pro847= (c.2541G>A) is classified Uncertain significance in UBE3A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-04). Very rare (popmax 8.48e-05%, nfe); Associated with Angelman syndrome.

What condition is associated with UBE3A p.Pro847= (c.2541G>A)?

UBE3A p.Pro847= (c.2541G>A) is associated with Angelman syndrome (ClinVar).

How common is UBE3A p.Pro847= (c.2541G>A) in the general population?

UBE3A p.Pro847= (c.2541G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

UBE3A p.Pro847=

c.2541G>A · VCV3608543

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Angelman syndrome

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.57	loss · gain 0.56 · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,176 alleles

Overall 6.21e-05% 1/1,611,320 alleles · very rare exomes 1/1,460,540 · genomes 0/150,780 · joint denominator

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: UBE3A
Protein: p.Pro847=
Coding: c.2541G>A
MANE Select: NM_130839
Type: single nucleotide variant
Location: chr15:25339215 (GRCh38)

Full UBE3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Angelman syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/ube3a-p-pro847 (accessed [today's date]).

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