Is USB1 p.Ter266Gly (c.796T>G) pathogenic?

USB1 p.Ter266Gly (c.796T>G) is classified Uncertain significance in USB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-06). Very rare (popmax 6.84e-05%); Associated with poikiloderma with neutropenia.

What condition is associated with USB1 p.Ter266Gly (c.796T>G)?

USB1 p.Ter266Gly (c.796T>G) is associated with poikiloderma with neutropenia (ClinVar).

How common is USB1 p.Ter266Gly (c.796T>G) in the general population?

USB1 p.Ter266Gly (c.796T>G) is very rare (popmax 6.84e-05%) (gnomAD).

How is Poikiloderma with neutropenia inherited?

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

USB1 p.Ter266Gly

c.796T>G · rs1963706554 · VCV1032181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

poikiloderma with neutropenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Overall
CADD	15.56	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,714 alleles · very rare

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: USB1
Protein: p.Ter266Gly
Coding: c.796T>G
MANE Select: NM_024598
dbSNP: rs1963706554
Type: single nucleotide variant
Location: chr16:58020243 (GRCh38)
Gene constraint: LOEUF 1.016 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.91 · 5 PDB

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 c.266-1G>A Pathogenic ★★ same condition
USB1 p.His208Arg Likely pathogenic ★★ same condition
USB1 p.Arg112Gln Uncertain significance ★★ ⚠ same condition
USB1 p.Arg245His Uncertain significance ★★ ⚠ same condition
USB1 p.Arg252Cys Uncertain significance ★★ ⚠ same condition
USB1 p.Arg70Gln Uncertain significance ★★ same condition
USB1 p.Arg70Trp Uncertain significance ★★ ⚠ same condition
USB1 p.Asn156His Uncertain significance ★★ ⚠ 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/usb1-p-ter266gly (accessed [today's date]).

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