Is UBE3A p.Arg7= (c.21A>G) pathogenic?

UBE3A p.Arg7= (c.21A>G) is classified Likely benign in UBE3A (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-01). Ultra-rare (popmax 0.0922%, sas).

How common is UBE3A p.Arg7= (c.21A>G) in the general population?

UBE3A p.Arg7= (c.21A>G) is ultra-rare (popmax 0.0922%, sas) (gnomAD).

UBE3A p.Arg7=

c.21A>G · rs752810430 · VCV516845

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0922%, sas)

⚠ 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 5	GERP 1.7, phastCons 1
Overall
CADD	17.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0922% South Asian · 84/91,064 alleles

Filtering AF 0.0763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0704%

Overall 0.00601% 97/1,613,818 alleles · ultra-rare exomes 89/1,461,622 · genomes 8/152,196 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0922%	1,084
Admixed American	0.0117%	8,574
Remaining individualsnot grpmax-eligible	0.0032%	31,247
European (non-Finnish)	0.000339%	294,967

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.Arg7=
Coding: c.21A>G
MANE Select: NM_130839
dbSNP: rs752810430
Type: single nucleotide variant
Location: chr15:25405502 (GRCh38)

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

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-arg7 (accessed [today's date]).

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