Is STS p.Pro146fs (c.437del) pathogenic?

STS p.Pro146fs (c.437del) is classified Likely pathogenic in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-20). No gnomAD frequency available for this variant; Associated with recessive X-linked ichthyosis.

What condition is associated with STS p.Pro146fs (c.437del)?

STS p.Pro146fs (c.437del) is associated with recessive X-linked ichthyosis (ClinVar).

How common is STS p.Pro146fs (c.437del) in the general population?

STS p.Pro146fs (c.437del) is no gnomAD frequency available for this variant (gnomAD).

How is Recessive X-linked ichthyosis inherited?

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

STS p.Pro146fs

c.437del · rs2147089236 · VCV1325152

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

recessive X-linked ichthyosis

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 8.9	GERP 6.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: STS
Protein: p.Pro146fs
Coding: c.437del
MANE Select: NM_001320752
dbSNP: rs2147089236
Type: Deletion
Location: chrX:7259401 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 146: a turn

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

Disease context

recessive X-linked ichthyosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Recessive X-linked ichthyosis (Orphanet):

Inheritance: X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

STS p.Pro146Ala Uncertain significance ★ ⚠ same residue
STS p.Gly354Arg Likely pathogenic ★★ same condition
STS c.259+8_259+10del Benign/Likely benign ★★ same condition
STS c.383-16C>T Benign/Likely benign ★★ same condition
STS c.1241+1G>C Likely pathogenic ★ same condition
STS c.806+1G>A Pathogenic ★ same condition
STS p.Gly128Arg Likely pathogenic ★ same condition
STS p.Gly370Cys Likely pathogenic ★ 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/sts-p-pro146fs (accessed [today's date]).

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