Is STS p.Cys136Arg (c.406T>C) pathogenic?

STS p.Cys136Arg (c.406T>C) is classified Uncertain significance in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely pathogenic (0.8283); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with STS p.Cys136Arg (c.406T>C)?

STS p.Cys136Arg (c.406T>C) is associated with Inborn genetic diseases (ClinVar).

How common is STS p.Cys136Arg (c.406T>C) in the general population?

STS p.Cys136Arg (c.406T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STS p.Cys136Arg (c.406T>C)?

AlphaMissense predicts likely pathogenic (score 0.8283) — an in-silico prediction, not a clinical call.

STS p.Cys136Arg

c.406T>C · VCV4177200

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8283 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8283	likely pathogenic
REVEL	0.801	moderately pathogenic-leaning
SaProt	LLR -12.05	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 6.3	GERP 6.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 72 kb · p 0.00048 · regional, not allelic
Overall
CADD	23.9	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 C141R vs ClinVar C136R) — 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.Cys136Arg
Coding: c.406T>C
MANE Select: NM_001320752
Type: single nucleotide variant
Location: chrX:7259372 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 136: an active site

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STS p.Arg381Ser Uncertain significance ★★ ⚠ same condition
STS p.Asp397Asn Uncertain significance ★★ ⚠ same condition
STS p.Arg578His Benign/Likely benign ★★ same condition
STS c.943+5G>A Conflicting classifications of pathogenicity ★ same condition
STS p.Ala295Val Uncertain significance ★ ⚠ same condition
STS p.Ala529Val Uncertain significance ★ ⚠ same condition
STS p.Arg179Ser Uncertain significance ★ ⚠ same condition
STS p.Arg233Pro 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-cys136arg (accessed [today's date]).

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