Is ATP2A3 p.Phe593= (c.1779C>T) pathogenic?

ATP2A3 p.Phe593= (c.1779C>T) is classified Likely benign in ATP2A3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Rare (popmax 0.41%, eas); Associated with ATP2A3-related disorder.

What condition is associated with ATP2A3 p.Phe593= (c.1779C>T)?

ATP2A3 p.Phe593= (c.1779C>T) is associated with ATP2A3-related disorder (ClinVar).

How common is ATP2A3 p.Phe593= (c.1779C>T) in the general population?

ATP2A3 p.Phe593= (c.1779C>T) is rare (popmax 0.41%, eas) (gnomAD).

ATP2A3 p.Phe593=

c.1779C>T · rs145904497 · VCV3050223

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.41%, eas)

Conditions

ATP2A3-related disorder

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 0.037	GERP 0.76, phastCons 0.37
Overall
CADD	13.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.41% East Asian · 184/44,870 alleles

Filtering AF 0.362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.343%

Overall 0.0181% 292/1,613,626 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.41%	244
South Asian	0.0648%	1,544
Remaining individualsnot grpmax-eligible	0.0448%	2,232
African / African-American	0.0107%	9,381
Admixed American	0.005%	20,009
Finnishnot grpmax-eligible	0.00157%	63,650
European (non-Finnish)	0.000763%	131,099

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: ATP2A3
Protein: p.Phe593=
Coding: c.1779C>T
MANE Select: NM_005173
dbSNP: rs145904497
Type: single nucleotide variant
Location: chr17:3941292 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.75

Full ATP2A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ATP2A3-related disorder

Similar variants

ATP2A3 c.1095+9C>T Likely benign same condition
ATP2A3 c.1419+10G>A Benign same condition
ATP2A3 c.1420-4G>A Likely benign same condition
ATP2A3 c.2863-5G>A Benign same condition
ATP2A3 c.*14A>G Benign same condition
ATP2A3 c.*19A>G Benign same condition
ATP2A3 p.Ala223= Likely benign same condition
ATP2A3 p.Ala331= Likely benign 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/atp2a3-p-phe593 (accessed [today's date]).

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