Is ATP2A1 p.Ile150= (c.450C>T) pathogenic?

ATP2A1 p.Ile150= (c.450C>T) is classified Conflicting classifications of pathogenicity in ATP2A1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-13). Ultra-rare (popmax 0.0164%, mid); Associated with Brody myopathy.

What condition is associated with ATP2A1 p.Ile150= (c.450C>T)?

ATP2A1 p.Ile150= (c.450C>T) is associated with Brody myopathy (ClinVar).

How common is ATP2A1 p.Ile150= (c.450C>T) in the general population?

ATP2A1 p.Ile150= (c.450C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Brody myopathy inherited?

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

ATP2A1 p.Ile150=

c.450C>T · rs781369773 · VCV318768

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Brody myopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.6
Overall
CADD	2.362	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00149% 24/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.004%	24,975
South Asian	0.0022%	45,540
Admixed American	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00136%	73,750

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: ATP2A1
Protein: p.Ile150=
Coding: c.450C>T
MANE Select: NM_004320
dbSNP: rs781369773
Type: single nucleotide variant
Location: chr16:28882576 (GRCh38)
Gene constraint: LOEUF 0.881 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.65

Full ATP2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Brody myopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

ATP2A1 p.Ile150Phe Uncertain significance ★ ⚠ same residue
ATP2A1 p.Ile150Val Uncertain significance ★ ⚠ same residue
ATP2A1 c.1184+1G>A Pathogenic/Likely pathogenic ★★ same condition
ATP2A1 c.2322-2A>G Likely pathogenic ★★ same condition
ATP2A1 c.2744+1G>A Likely pathogenic ★★ same condition
ATP2A1 c.2862+1G>A Pathogenic/Likely pathogenic ★★ same condition
ATP2A1 c.324+1G>A Pathogenic/Likely pathogenic ★★ same condition
ATP2A1 c.325-2A>T Pathogenic/Likely pathogenic ★★ 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/atp2a1-p-ile150 (accessed [today's date]).

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