Is UBE3A p.Ser85Phe (c.254C>T) pathogenic?

UBE3A p.Ser85Phe (c.254C>T) is classified Uncertain significance in UBE3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.8883); Absent from gnomAD v4.1; Associated with Angelman syndrome.

What condition is associated with UBE3A p.Ser85Phe (c.254C>T)?

UBE3A p.Ser85Phe (c.254C>T) is associated with Angelman syndrome (ClinVar).

How common is UBE3A p.Ser85Phe (c.254C>T) in the general population?

UBE3A p.Ser85Phe (c.254C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UBE3A p.Ser85Phe (c.254C>T)?

AlphaMissense predicts likely pathogenic (score 0.8883) — an in-silico prediction, not a clinical call.

UBE3A p.Ser85Phe

c.254C>T · VCV4802382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8883 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

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
AlphaMissense	0.8883	likely pathogenic
REVEL	0.318	indeterminate
SaProt	LLR -7.81	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 122 bp · p 1.8e-05 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S88F vs ClinVar S85F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UBE3A
Protein: p.Ser85Phe
Coding: c.254C>T
MANE Select: NM_130839
Type: single nucleotide variant
Location: chr15:25375572 (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-ser85phe (accessed [today's date]).

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