Is USB1 p.Pro60fs (c.179del) pathogenic?

USB1 p.Pro60fs (c.179del) is classified Pathogenic in USB1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2010-06-01). Absent from gnomAD; Associated with poikiloderma with neutropenia.

What condition is associated with USB1 p.Pro60fs (c.179del)?

USB1 p.Pro60fs (c.179del) is associated with poikiloderma with neutropenia (ClinVar).

How common is USB1 p.Pro60fs (c.179del) in the general population?

USB1 p.Pro60fs (c.179del) is absent from gnomAD (gnomAD).

How is Poikiloderma with neutropenia inherited?

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

USB1 p.Pro60fs

c.179del · rs786205051 · VCV18399

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

poikiloderma with neutropenia

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 2 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.13	GERP -0.63, phastCons 0.002

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: USB1
Protein: p.Pro60fs
Coding: c.179del
MANE Select: NM_024598
dbSNP: rs786205051
Type: Deletion
Location: chr16:58002558 (GRCh38)
Gene constraint: LOEUF 1.016 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.91 · 5 PDB
Residue 60: the 'disordered' region

Full USB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

poikiloderma with neutropenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Poikiloderma with neutropenia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

USB1 p.Met22fs Pathogenic/Likely pathogenic ★★ same condition
USB1 p.Arg115_Met116insTer Likely pathogenic ★ same condition
USB1 p.Asn163fs Pathogenic ★ same condition
USB1 p.Gly59fs Pathogenic ★ same condition
USB1 p.Thr167fs Pathogenic ★ same condition
USB1 p.Pro60Leu Uncertain significance ★ ⚠ same residue
USB1 p.Pro60Ser Uncertain significance ★ ⚠ same residue
USB1 p.Pro60Thr Uncertain significance ★ ⚠ same residue

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/usb1-p-pro60fs (accessed [today's date]).

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