UBE3A p.Ser355=
c.1065T>C · rs2552191640 · VCV2645013
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2 | GERP -3.5, phastCons 1 |
| Overall | ||
| CADD | 7.618 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/75,016 alleles
Filtering AF
0.000442%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000186%
3/1,614,072 alleles · very rare
exomes 3/1,461,826 · genomes 0/152,246 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,508 |
| European (non-Finnish) | 8.47e-05% | 1,180,012 |
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.Ser355=
- Coding
- c.1065T>C
- MANE Select
- NM_130839
- dbSNP
- rs2552191640
- Type
- single nucleotide variant
- Location
- chr15:25371109 (GRCh38)
- Gene constraint
- LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 81.42 · 25 PDB
Similar variants
- UBE3A p.Ser355Thr Benign ★★★ same residue
- UBE3A c.2125-1G>A Likely pathogenic ★★★ same type
- UBE3A p.Arg526Cys Pathogenic ★★★ same type
- UBE3A p.Gly870Asp Likely pathogenic ★★★ same type
- UBE3A c.1609-8A>G Uncertain significance ★★★ same type
- UBE3A p.Asn581Ser Uncertain significance ★★★ ⚠ same type
- UBE3A p.Cys137Arg Uncertain significance ★★★ ⚠ same type
- UBE3A p.Phe805= 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/ube3a-p-ser355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown