Is STS p.Trp367Arg (c.1099T>A) pathogenic?

STS p.Trp367Arg (c.1099T>A) is classified Pathogenic in STS (ClinVar, No assertion criteria, 1 submitter; last evaluated 1997-08-15). AlphaMissense: likely pathogenic (0.9377); Absent from gnomAD v4.1; Associated with recessive X-linked ichthyosis.

What condition is associated with STS p.Trp367Arg (c.1099T>A)?

STS p.Trp367Arg (c.1099T>A) is associated with recessive X-linked ichthyosis (ClinVar).

How common is STS p.Trp367Arg (c.1099T>A) in the general population?

STS p.Trp367Arg (c.1099T>A) is absent from gnomAD v4.1 (gnomAD).

How is Recessive X-linked ichthyosis inherited?

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

What do computational predictors say about STS p.Trp367Arg (c.1099T>A)?

AlphaMissense predicts likely pathogenic (score 0.9377) — an in-silico prediction, not a clinical call.

STS p.Trp367Arg

c.1099T>A · rs137853165 · VCV10552

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9377 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

recessive X-linked ichthyosis

Computational evidence

Protein change
AlphaMissense	0.9377	likely pathogenic ✓ concordant with ClinVar · top 7% in STS
REVEL	0.881	moderately pathogenic-leaning
SaProt	LLR -14.58	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 6.2	GERP 6.4, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 25 kb · p 0.038 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM W372R vs ClinVar W367R) — verify the residue.

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: STS
Protein: p.Trp367Arg
Coding: c.1099T>A
MANE Select: NM_001320752
dbSNP: rs137853165
Type: single nucleotide variant
Location: chrX:7325356 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 372 UniProt numbering: a UniProt-annotated variant site (in ixl; loss of steryl-sulfatase activity); a β-strand

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.Trp367Ser Uncertain significance ★ ⚠ same residue
STS p.Trp367Cys Uncertain significance ★ ⚠ same residue
STS p.Gly354Arg Likely pathogenic ★★ 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-trp367arg (accessed [today's date]).

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