Is USB1 p.Leu129= (c.387G>C) pathogenic?

USB1 p.Leu129= (c.387G>C) is classified Likely benign in USB1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-07). Ultra-rare (popmax 0.067%, sas); Associated with Inborn genetic diseases.

What condition is associated with USB1 p.Leu129= (c.387G>C)?

USB1 p.Leu129= (c.387G>C) is associated with Inborn genetic diseases, poikiloderma with neutropenia (ClinVar).

How common is USB1 p.Leu129= (c.387G>C) in the general population?

USB1 p.Leu129= (c.387G>C) is ultra-rare (popmax 0.067%, sas) (gnomAD).

USB1 p.Leu129=

c.387G>C · rs542658449 · VCV1597679

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.067%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -2, phastCons 1
Overall
CADD	7.075	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.067% South Asian · 61/91,082 alleles

Filtering AF 0.0535% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0486%

Overall 0.00415% 67/1,614,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.067%	1,493
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.000339%	295,005

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.Leu129=
Coding: c.387G>C
MANE Select: NM_024598
dbSNP: rs542658449
Type: single nucleotide variant
Location: chr16:58010050 (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 129: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: poikiloderma with neutropenia

Similar variants

USB1 c.266-1G>A Pathogenic ★★ same condition
USB1 p.His208Arg Likely pathogenic ★★ same condition
USB1 p.Ala106Ser Uncertain significance ★★ ⚠ same condition
USB1 p.Ala218Thr Uncertain significance ★★ ⚠ same condition
USB1 p.Ala218Val Uncertain significance ★★ ⚠ same condition
USB1 p.Arg112Gln Uncertain significance ★★ ⚠ same condition
USB1 p.Arg112Trp Uncertain significance ★★ ⚠ same condition
USB1 p.Arg130Cys 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-leu129 (accessed [today's date]).

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