Is STS p.Arg81Trp (c.241C>T) pathogenic?

STS p.Arg81Trp (c.241C>T) is classified Conflicting classifications of pathogenicity in STS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-04). AlphaMissense: likely pathogenic (0.7932); Very rare (popmax 0.000112%, nfe); Associated with recessive X-linked ichthyosis.

What condition is associated with STS p.Arg81Trp (c.241C>T)?

STS p.Arg81Trp (c.241C>T) is associated with recessive X-linked ichthyosis (ClinVar).

How common is STS p.Arg81Trp (c.241C>T) in the general population?

STS p.Arg81Trp (c.241C>T) is very rare (popmax 0.000112%, 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.Arg81Trp (c.241C>T)?

AlphaMissense predicts likely pathogenic (score 0.7932) — an in-silico prediction, not a clinical call.

STS p.Arg81Trp

c.241C>T · rs1259321805 · VCV1683504

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

recessive X-linked ichthyosis

Computational evidence

Protein change
AlphaMissense	0.7932	likely pathogenic
REVEL	0.781	moderately pathogenic-leaning
SaProt	LLR -14.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.85 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP 3.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 72 kb · p 0.00048 · 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 R86W vs ClinVar R81W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,317 alleles

Overall 8.25e-05% 1/1,211,707 alleles · very rare exomes 1/1,097,840 · genomes 0/113,867 · 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.Arg81Trp
Coding: c.241C>T
MANE Select: NM_001320752
dbSNP: rs1259321805
Type: single nucleotide variant
Location: chrX:7257345 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB

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.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
STS p.Trp91Ter Pathogenic ★ same condition
STS c.1082-18T>C 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/sts-p-arg81trp (accessed [today's date]).

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