Is STIM1 p.Arg287Cys (c.859C>T) pathogenic?

STIM1 p.Arg287Cys (c.859C>T) is classified Uncertain significance in STIM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-15). AlphaMissense: likely benign (0.3047); Very rare (popmax 0.00801%, afr); Associated with tubular aggregate myopathy.

What condition is associated with STIM1 p.Arg287Cys (c.859C>T)?

STIM1 p.Arg287Cys (c.859C>T) is associated with tubular aggregate myopathy, Stormorken syndrome, combined immunodeficiency due to STIM1 deficiency (ClinVar).

How common is STIM1 p.Arg287Cys (c.859C>T) in the general population?

STIM1 p.Arg287Cys (c.859C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

How is Tubular aggregate myopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about STIM1 p.Arg287Cys (c.859C>T)?

AlphaMissense predicts likely benign (score 0.3047) — an in-silico prediction, not a clinical call.

STIM1 p.Arg287Cys

c.859C>T · rs1034949340 · VCV951660

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3047 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

tubular aggregate myopathy

Computational evidence

Protein change
AlphaMissense	0.3047	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -9.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP -0.23, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 13 kb · p 8.6e-12 · regional, not allelic
Overall
CADD	32.0	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,896 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000867% 14/1,613,890 alleles · very rare exomes 11/1,461,756 · genomes 3/152,134 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,483
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000593%	168,571

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: STIM1
Protein: p.Arg287Cys
Coding: c.859C>T
MANE Select: NM_001382567
dbSNP: rs1034949340
Type: single nucleotide variant
Location: chr11:4074569 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 6 PDB
Residue 287: an α-helix

Full STIM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tubular aggregate myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Stormorken syndrome combined immunodeficiency due to STIM1 deficiency

For Tubular aggregate myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

STIM1 p.Arg287= Benign/Likely benign ★★ same residue
STIM1 p.Arg287His Uncertain significance ★ ⚠ same residue
STIM1 p.Arg287Ser Uncertain significance ★ ⚠ same residue
STIM1 p.Arg304Trp Pathogenic ★★ ⚠ same condition
STIM1 p.Arg50Ter Pathogenic/Likely pathogenic ★★ same condition
STIM1 p.His109Arg Pathogenic/Likely pathogenic ★★ same condition
STIM1 p.Ser88Gly Pathogenic/Likely pathogenic ★★ same condition
STIM1 c.792-3C>A 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/stim1-p-arg287cys (accessed [today's date]).

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