Is UBE3A p.Ser97= (c.291G>A) pathogenic?

UBE3A p.Ser97= (c.291G>A) is classified Likely benign in UBE3A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-13). Ultra-rare (popmax 0.012%, afr); Associated with Angelman syndrome.

What condition is associated with UBE3A p.Ser97= (c.291G>A)?

UBE3A p.Ser97= (c.291G>A) is associated with Angelman syndrome (ClinVar).

How common is UBE3A p.Ser97= (c.291G>A) in the general population?

UBE3A p.Ser97= (c.291G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

UBE3A p.Ser97=

c.291G>A · rs1411368065 · VCV766757

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

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
Constraint at this position
Conservation	phyloP -4.7	GERP -3.8
Overall
CADD	7.645	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,920 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.000867% 14/1,614,042 alleles · ultra-rare exomes 10/1,461,878 · genomes 4/152,164 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,324
Remaining individualsnot grpmax-eligible	0.0016%	62,484
South Asian	0.0011%	91,078
European (non-Finnish)	0.000254%	393,349

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.Ser97=
Coding: c.291G>A
MANE Select: NM_130839
dbSNP: rs1411368065
Type: single nucleotide variant
Location: chr15:25375535 (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-ser97 (accessed [today's date]).

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