Is STIM1 p.Ser552= (c.1656G>A) pathogenic?

STIM1 p.Ser552= (c.1656G>A) is classified Likely benign in STIM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). Ultra-rare (popmax 0.011%, sas); Associated with combined immunodeficiency due to STIM1 deficiency.

What condition is associated with STIM1 p.Ser552= (c.1656G>A)?

STIM1 p.Ser552= (c.1656G>A) is associated with combined immunodeficiency due to STIM1 deficiency, tubular aggregate myopathy, Stormorken syndrome (ClinVar).

How common is STIM1 p.Ser552= (c.1656G>A) in the general population?

STIM1 p.Ser552= (c.1656G>A) is ultra-rare (popmax 0.011%, sas) (gnomAD).

STIM1 p.Ser552=

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.1656G>A · rs148209416 · VCV1064085

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, 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	0.306	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Overall
CADD	15.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,080 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00483% 78/1,613,932 alleles · ultra-rare exomes 75/1,461,870 · genomes 3/152,062 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,108
East Asian	0.00891%	11,223
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.00483%	20,702
African / African-American	0.00267%	37,438
Admixed American	0.00167%	59,986

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.Ser552=
Coding: c.1656G>A
MANE Select: NM_001382567
dbSNP: rs148209416
Type: single nucleotide variant
Location: chr11:4091303 (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.Ser552Leu 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
STIM1 p.Ala163Asp 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-ser552 (accessed [today's date]).

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