Is STS p.Trp91Ter (c.272G>A) pathogenic?

STS p.Trp91Ter (c.272G>A) is classified Pathogenic in STS (ClinVar, Single submitter, 2 submitters; last evaluated 2019-04-30). Absent from gnomAD v4.1; Associated with recessive X-linked ichthyosis.

What condition is associated with STS p.Trp91Ter (c.272G>A)?

STS p.Trp91Ter (c.272G>A) is associated with recessive X-linked ichthyosis (ClinVar).

How common is STS p.Trp91Ter (c.272G>A) in the general population?

STS p.Trp91Ter (c.272G>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.

STS p.Trp91Ter

c.272G>A · rs1463414987 · VCV625856

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

recessive X-linked ichthyosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.26	loss · gain 0.23 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -1.3	GERP -6.1
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

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

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.Trp91Ter
Coding: c.272G>A
MANE Select: NM_001320752
dbSNP: rs1463414987
Type: single nucleotide variant
Location: chrX:7257478 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 91: an α-helix

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 c.1082-18T>C Uncertain significance ★ same condition
STS p.Arg269Gln 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-trp91ter (accessed [today's date]).

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