Is USP53 p.Val279fs (c.834_835dup) pathogenic?

USP53 p.Val279fs (c.834835dup) is classified Pathogenic in USP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-15). No gnomAD frequency available for this variant; Associated with cholestasis.

What condition is associated with USP53 p.Val279fs (c.834_835dup)?

USP53 p.Val279fs (c.834_835dup) is associated with cholestasis (ClinVar).

How common is USP53 p.Val279fs (c.834_835dup) in the general population?

USP53 p.Val279fs (c.834_835dup) is no gnomAD frequency available for this variant (gnomAD).

USP53 p.Val279fs

c.834_835dup · rs1578504946 · VCV694478

Pathogenic Single submitter

Classification

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

cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.19	GERP -3.9, phastCons 0.67

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: USP53
Protein: p.Val279fs
Coding: c.834_835dup
MANE Select: NM_001371395
dbSNP: rs1578504946
Type: Microsatellite
Location: chr4:119261723 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.34
Residue 279: the usp domain; a UniProt-annotated variant site (in pfic7)

Full USP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cholestasis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USP53 p.Arg338Ter Pathogenic ★★ same condition
USP53 p.Arg476Ter Pathogenic/Likely pathogenic ★★ same condition
USP53 p.Arg520Ter Pathogenic ★★ same condition
USP53 c.569+2T>C Pathogenic ★ same condition
USP53 p.Arg195fs Pathogenic ★ same condition
USP53 p.Arg57Ter Pathogenic ★ same condition
USP53 p.Arg99Ser Pathogenic ★ same condition
USP53 p.Gly293Val 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/usp53-p-val279fs (accessed [today's date]).

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