Is UBE2A p.Val141fs (c.421_422del) pathogenic?

UBE2A p.Val141fs (c.421422del) is classified Likely pathogenic in UBE2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). No gnomAD frequency available for this variant; Associated with syndromic X-linked intellectual disability Nascimento type.

What condition is associated with UBE2A p.Val141fs (c.421_422del)?

UBE2A p.Val141fs (c.421_422del) is associated with syndromic X-linked intellectual disability Nascimento type (ClinVar).

How common is UBE2A p.Val141fs (c.421_422del) in the general population?

UBE2A p.Val141fs (c.421_422del) is no gnomAD frequency available for this variant (gnomAD).

UBE2A p.Val141fs

Q: How is X-linked intellectual disability, Nascimento type inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.421_422del · rs2147382084 · VCV1333497

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

syndromic X-linked intellectual disability Nascimento type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: UBE2A
Protein: p.Val141fs
Coding: c.421_422del
MANE Select: NM_003336
dbSNP: rs2147382084
Type: Microsatellite
Location: chrX:119583215 (GRCh38)
Structure: AlphaFold pLDDT 94.25 · 5 PDB
Residue 141: the ubc core domain; a UniProt-annotated variant site (in mrxsn); an α-helix

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

Disease context

syndromic X-linked intellectual disability Nascimento type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked intellectual disability, Nascimento type (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy

Similar variants

UBE2A p.Asp101del Likely pathogenic ★★ same condition
UBE2A p.Arg135Trp Uncertain significance ★★ ⚠ same condition
UBE2A p.Arg95Cys Uncertain significance ★★ ⚠ same condition
UBE2A c.125+1G>T Likely pathogenic ★ same condition
UBE2A c.126-2A>G Pathogenic ★ same condition
UBE2A c.242-3_244del Likely pathogenic ★ same condition
UBE2A c.330+1del Likely pathogenic ★ same condition
UBE2A c.330+1G>A Likely pathogenic ★ 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/ube2a-p-val141fs (accessed [today's date]).

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