Is STIM1 p.Phe439= (c.1317C>T) pathogenic?

STIM1 p.Phe439= (c.1317C>T) is classified Likely benign in STIM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-15). Very rare (popmax 0.0011%, sas); Associated with tubular aggregate myopathy.

What condition is associated with STIM1 p.Phe439= (c.1317C>T)?

STIM1 p.Phe439= (c.1317C>T) is associated with tubular aggregate myopathy, Stormorken syndrome, combined immunodeficiency due to STIM1 deficiency (ClinVar).

How common is STIM1 p.Phe439= (c.1317C>T) in the general population?

STIM1 p.Phe439= (c.1317C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Tubular aggregate myopathy inherited?

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

STIM1 p.Phe439=

c.1317C>T · rs1179975549 · VCV1622505

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

tubular aggregate myopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.8	GERP 1.9, phastCons 1
Overall
CADD	16.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,246 alleles · very rare exomes 3/1,461,894 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	0.000169%	590,023

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.Phe439=
Coding: c.1317C>T
MANE Select: NM_001382567
dbSNP: rs1179975549
Type: single nucleotide variant
Location: chr11:4083341 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 6 PDB
Residue 439: the 'soar/cad' region

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.Phe439Leu 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-phe439 (accessed [today's date]).

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