Is STIM1 p.Pro487= (c.1461C>T) pathogenic?

STIM1 p.Pro487= (c.1461C>T) is classified Likely benign in STIM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-25). Very rare (popmax 0.0044%, sas); Associated with combined immunodeficiency due to STIM1 deficiency.

What condition is associated with STIM1 p.Pro487= (c.1461C>T)?

STIM1 p.Pro487= (c.1461C>T) is associated with combined immunodeficiency due to STIM1 deficiency, tubular aggregate myopathy, Stormorken syndrome (ClinVar).

How common is STIM1 p.Pro487= (c.1461C>T) in the general population?

STIM1 p.Pro487= (c.1461C>T) is very rare (popmax 0.0044%, sas) (gnomAD).

STIM1 p.Pro487=

Q: How is Combined immunodeficiency due to CRAC channel dysfunction inherited?

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

c.1461C>T · rs751169800 · VCV1541149

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Conditions

combined immunodeficiency due to STIM1 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.541	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.003	GERP -3.2, phastCons 0.72
Overall
CADD	8.523	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0044% South Asian · 4/90,982 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0018% 29/1,613,616 alleles · very rare exomes 22/1,461,382 · genomes 7/152,234 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,746
Admixed American	0.00334%	29,982
European (non-Finnish)	0.00178%	56,179
Remaining individualsnot grpmax-eligible	0.0016%	62,472
African / African-American	0.00133%	74,942

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.Pro487=
Coding: c.1461C>T
MANE Select: NM_001382567
dbSNP: rs751169800
Type: single nucleotide variant
Location: chr11:4083485 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 6 PDB

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

Disease context

combined immunodeficiency due to STIM1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tubular aggregate myopathy Stormorken syndrome

For Combined immunodeficiency due to CRAC channel dysfunction (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

STIM1 p.Pro487Ala Uncertain significance ★ ⚠ same residue
STIM1 p.Pro487Ser 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
STIM1 c.792-3C>G 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-pro487 (accessed [today's date]).

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