Is USB1 p.Ser124Pro (c.370T>C) pathogenic?

USB1 p.Ser124Pro (c.370T>C) is classified Likely pathogenic in USB1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-26). AlphaMissense: likely pathogenic (0.97); Absent from gnomAD v4.1; Associated with poikiloderma with neutropenia.

What condition is associated with USB1 p.Ser124Pro (c.370T>C)?

USB1 p.Ser124Pro (c.370T>C) is associated with poikiloderma with neutropenia (ClinVar).

How common is USB1 p.Ser124Pro (c.370T>C) in the general population?

USB1 p.Ser124Pro (c.370T>C) 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.Ser124Pro (c.370T>C)?

AlphaMissense predicts likely pathogenic (score 0.97) — an in-silico prediction, not a clinical call.

USB1 p.Ser124Pro

c.370T>C · rs1597049287 · VCV800958

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.97 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

poikiloderma with neutropenia

Computational evidence

Protein change
AlphaMissense	0.97	likely pathogenic ✓ concordant with ClinVar · top 1% in USB1
REVEL	0.776	moderately pathogenic-leaning
SaProt	LLR -15.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.36 · regional, not allelic
Overall
CADD	29.1	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.Ser124Pro
Coding: c.370T>C
MANE Select: NM_024598
dbSNP: rs1597049287
Type: single nucleotide variant
Location: chr16:58010033 (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 p.Ser124= Likely benign ★★ same residue
USB1 p.Ser124Cys Uncertain significance ★ ⚠ same residue
USB1 p.Ser124Phe Uncertain significance ★ ⚠ 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
USB1 p.Arg252Cys 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-ser124pro (accessed [today's date]).

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