Is STS p.Leu159fs (c.475_476del) pathogenic?

STS p.Leu159fs (c.475476del) is classified Likely pathogenic in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2017-07-13). Associated with STS-related disorder.

What condition is associated with STS p.Leu159fs (c.475_476del)?

STS p.Leu159fs (c.475_476del) is associated with STS-related disorder (ClinVar).

STS p.Leu159fs

c.475_476del · VCV4948676

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

STS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.5	GERP 6.7, phastCons 0.11

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

Variant & gene context

Gene: STS
Protein: p.Leu159fs
Coding: c.475_476del
MANE Select: NM_001320752
Type: Deletion
Location: chrX:7259440 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 159: a β-strand

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

Disease context

STS-related disorder

Similar variants

STS p.Leu53fs Likely pathogenic ★ same condition
STS p.Phe212fs Likely pathogenic ★ same condition
STS p.Arg449His Likely pathogenic ★ same condition
STS p.Gly354Ter Likely pathogenic ★ same condition
STS p.His131Tyr Likely pathogenic ★ same condition
STS p.Pro68Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
STS p.Arg21fs Likely pathogenic ★ same type
STS p.Pro146fs Likely pathogenic ★ same type

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/sts-p-leu159fs (accessed [today's date]).

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