Is UBE2A p.Val81= (c.243C>A) pathogenic?

UBE2A p.Val81= (c.243C>A) is classified Likely benign in UBE2A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-16). Rare (popmax 0.126%, sas); Associated with UBE2A-related disorder.

What condition is associated with UBE2A p.Val81= (c.243C>A)?

UBE2A p.Val81= (c.243C>A) is associated with UBE2A-related disorder (ClinVar).

How common is UBE2A p.Val81= (c.243C>A) in the general population?

UBE2A p.Val81= (c.243C>A) is rare (popmax 0.126%, sas) (gnomAD).

UBE2A p.Val81=

c.243C>A · rs764875570 · VCV3048481

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.126%, sas)

Conditions

UBE2A-related disorder

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 0.26	GERP -2.2, phastCons 0.98
Overall
CADD	8.955	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.126% South Asian · 71/56,450 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0936%

Overall 0.00634% 76/1,198,021 alleles · rare exomes 69/1,085,966 · genomes 7/112,055 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.126%	795
Remaining individualsnot grpmax-eligible	0.00848%	11,793
European (non-Finnish)	0.000113%	884,846

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: UBE2A
Protein: p.Val81=
Coding: c.243C>A
MANE Select: NM_003336
dbSNP: rs764875570
Type: single nucleotide variant
Location: chrX:119582589 (GRCh38)
Structure: AlphaFold pLDDT 94.25 · 5 PDB
Residue 81: the ubc core domain

Full UBE2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

UBE2A-related disorder

Similar variants

UBE2A p.Val81Asp Uncertain significance ★ ⚠ same residue
UBE2A p.Val81Ile Uncertain significance ★ ⚠ same residue
UBE2A c.330+1G>A Likely pathogenic ★ same condition
UBE2A c.331-1G>A Likely pathogenic ★ same condition
UBE2A p.Arg135Trp Uncertain significance ★★ ⚠ same type
UBE2A p.Arg95Cys Uncertain significance ★★ ⚠ same type
UBE2A p.Ile57Val Uncertain significance ★★ ⚠ same type
UBE2A c.125+14C>T Benign/Likely benign ★★ 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/ube2a-p-val81 (accessed [today's date]).

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