Is STS p.Arg93His (c.278G>A) pathogenic?

STS p.Arg93His (c.278G>A) is classified Uncertain significance in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1114); Rare (popmax 0.11%, afr); Associated with Inborn genetic diseases.

What condition is associated with STS p.Arg93His (c.278G>A)?

STS p.Arg93His (c.278G>A) is associated with Inborn genetic diseases (ClinVar).

How common is STS p.Arg93His (c.278G>A) in the general population?

STS p.Arg93His (c.278G>A) is rare (popmax 0.11%, afr) (gnomAD).

What do computational predictors say about STS p.Arg93His (c.278G>A)?

AlphaMissense predicts likely benign (score 0.1114) — an in-silico prediction, not a clinical call.

STS p.Arg93His

c.278G>A · VCV4177195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1114 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.11%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1114	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.36	acceptor gain · deltas
Pangolin	Δ0.46	gain · loss 0.33 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.36	GERP -0.6
Regional constraint	o/e 0.79	unconstrained · MANE · 72 kb · p 0.00048 · regional, not allelic
Overall
CADD	15.77	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 R98H vs ClinVar R93H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.11% African / African-American · 63/57,498 alleles

Filtering AF 0.0879% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.08%

Overall 0.00735% 89/1,210,871 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.11%	913
Middle Eastern	0.023%	4,354
Admixed American	0.0218%	4,592
Remaining individualsnot grpmax-eligible	0.0189%	5,292
East Asian	0.00296%	33,763
European (non-Finnish)	0.000558%	179,068

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.Arg93His
Coding: c.278G>A
MANE Select: NM_001320752
Type: single nucleotide variant
Location: chrX:7257484 (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.Arg93Cys 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-arg93his (accessed [today's date]).

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