Is STS p.Arg93Cys (c.277C>T) pathogenic?

STS p.Arg93Cys (c.277C>T) is classified Uncertain significance in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: ambiguous (0.3727); Very rare (popmax 0.00296%, eas); Associated with Inborn genetic diseases.

What condition is associated with STS p.Arg93Cys (c.277C>T)?

STS p.Arg93Cys (c.277C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STS p.Arg93Cys (c.277C>T) in the general population?

STS p.Arg93Cys (c.277C>T) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about STS p.Arg93Cys (c.277C>T)?

AlphaMissense predicts ambiguous (score 0.3727) — an in-silico prediction, not a clinical call.

STS p.Arg93Cys

c.277C>T · rs779329015 · VCV2218593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3727 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3727	ambiguous
REVEL	0.327	indeterminate
SaProt	LLR -9.99	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.7	GERP 1.2
Regional constraint	o/e 0.79	unconstrained · MANE · 72 kb · p 0.00048 · regional, not allelic
Overall
CADD	16.35	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 R98C vs ClinVar R93C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,776 alleles

Filtering AF 0.00126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00182% 22/1,210,899 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0042%	23,803
East Asiangrpmax	0.00296%	33,776
Admixed American	0.00218%	45,923
European (non-Finnish)	0.00201%	49,742

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg93Cys
Coding: c.277C>T
MANE Select: NM_001320752
dbSNP: rs779329015
Type: single nucleotide variant
Location: chrX:7257483 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB

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.Arg93His Uncertain significance ★ ⚠ same residue
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

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-arg93cys (accessed [today's date]).

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