Is STS p.Trp367Ser (c.1100G>C) pathogenic?

STS p.Trp367Ser (c.1100G>C) is classified Uncertain significance in STS (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-17). AlphaMissense: likely pathogenic (0.7372); Very rare (popmax 0.000223%, nfe); Associated with recessive X-linked ichthyosis.

What condition is associated with STS p.Trp367Ser (c.1100G>C)?

STS p.Trp367Ser (c.1100G>C) is associated with recessive X-linked ichthyosis (ClinVar).

How common is STS p.Trp367Ser (c.1100G>C) in the general population?

STS p.Trp367Ser (c.1100G>C) is very rare (popmax 0.000223%, nfe) (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.Trp367Ser (c.1100G>C)?

AlphaMissense predicts likely pathogenic (score 0.7372) — an in-silico prediction, not a clinical call.

STS p.Trp367Ser

c.1100G>C · rs137853168 · VCV10555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7372 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000223%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

recessive X-linked ichthyosis

Computational evidence

Protein change
AlphaMissense	0.7372	likely pathogenic
REVEL	0.886	moderately pathogenic-leaning
SaProt	LLR -16.28	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 6.4, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 25 kb · p 0.038 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM W372S vs ClinVar W367S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000223% European (non-Finnish) · 2/895,281 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000165% 2/1,211,315 alleles · very rare exomes 2/1,097,939 · genomes 0/113,376 · joint denominator

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: STS
Protein: p.Trp367Ser
Coding: c.1100G>C
MANE Select: NM_001320752
dbSNP: rs137853168
Type: single nucleotide variant
Location: chrX:7325357 (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.Trp367Arg Pathogenic 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-trp367ser (accessed [today's date]).

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