Is USB1 p.Pro205Ser (c.613C>T) pathogenic?

USB1 p.Pro205Ser (c.613C>T) is classified Uncertain significance in USB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-14). AlphaMissense: ambiguous (0.4952); Absent from gnomAD v4.1; Associated with poikiloderma with neutropenia.

What condition is associated with USB1 p.Pro205Ser (c.613C>T)?

USB1 p.Pro205Ser (c.613C>T) is associated with poikiloderma with neutropenia (ClinVar).

How common is USB1 p.Pro205Ser (c.613C>T) in the general population?

USB1 p.Pro205Ser (c.613C>T) is absent from gnomAD v4.1 (gnomAD).

How is Poikiloderma with neutropenia inherited?

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

What do computational predictors say about USB1 p.Pro205Ser (c.613C>T)?

AlphaMissense predicts ambiguous (score 0.4952) — an in-silico prediction, not a clinical call.

USB1 p.Pro205Ser

c.613C>T · VCV4850846

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4952 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

poikiloderma with neutropenia

Computational evidence

Protein change
AlphaMissense	0.4952	ambiguous
REVEL	0.477	indeterminate
SaProt	LLR -12.38	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.36 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: USB1
Protein: p.Pro205Ser
Coding: c.613C>T
MANE Select: NM_024598
Type: single nucleotide variant
Location: chr16:58018975 (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 205: a binding site

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.Pro205Arg Uncertain significance ★ same residue
USB1 p.Pro205Leu Uncertain significance ★ same residue
USB1 p.Pro205Thr Uncertain significance ★ same residue
USB1 p.Pro205= Likely benign ★ same residue
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

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-pro205ser (accessed [today's date]).

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