Is UBE3A p.Pro600= (c.1800A>G) pathogenic?

UBE3A p.Pro600= (c.1800A>G) is classified Likely benign in UBE3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). Very rare (popmax 0.0022%, sas); Associated with Angelman syndrome.

What condition is associated with UBE3A p.Pro600= (c.1800A>G)?

UBE3A p.Pro600= (c.1800A>G) is associated with Angelman syndrome (ClinVar).

How common is UBE3A p.Pro600= (c.1800A>G) in the general population?

UBE3A p.Pro600= (c.1800A>G) is very rare (popmax 0.0022%, sas) (gnomAD).

UBE3A p.Pro600=

c.1800A>G · rs754664908 · VCV1141879

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Angelman syndrome

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 -1.2	GERP -3.5, phastCons 0.001
Overall
CADD	7.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,074 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000248% 4/1,613,784 alleles · very rare exomes 4/1,461,530 · genomes 0/152,254 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,537
European (non-Finnish)	0.00017%	589,915

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.Pro600=
Coding: c.1800A>G
MANE Select: NM_130839
dbSNP: rs754664908
Type: single nucleotide variant
Location: chr15:25356850 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.42 · 25 PDB
Residue 600: a β-strand

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

Similar variants

UBE3A c.2125-1G>A Likely pathogenic ★★★ same condition
UBE3A p.Arg526Cys Pathogenic ★★★ same condition
UBE3A p.Gly870Asp Likely pathogenic ★★★ same condition
UBE3A c.1609-8A>G Uncertain significance ★★★ same condition
UBE3A p.Asn581Ser Uncertain significance ★★★ ⚠ same condition
UBE3A p.Cys137Arg Uncertain significance ★★★ ⚠ same condition
UBE3A p.Phe805= Uncertain significance ★★★ same condition
UBE3A p.Thr807Ala Uncertain significance ★★★ ⚠ same condition

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-pro600 (accessed [today's date]).

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