Is ATP2A3 p.Ala331= (c.993C>T) pathogenic?

ATP2A3 p.Ala331= (c.993C>T) is classified Likely benign in ATP2A3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Rare (popmax 0.214%, eas); Associated with ATP2A3-related disorder.

What condition is associated with ATP2A3 p.Ala331= (c.993C>T)?

ATP2A3 p.Ala331= (c.993C>T) is associated with ATP2A3-related disorder (ClinVar).

How common is ATP2A3 p.Ala331= (c.993C>T) in the general population?

ATP2A3 p.Ala331= (c.993C>T) is rare (popmax 0.214%, eas) (gnomAD).

ATP2A3 p.Ala331=

c.993C>T · rs183496663 · VCV3050132

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.214%, 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 3.5	GERP -3.2, phastCons 1
Overall
CADD	8.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.214% East Asian · 96/44,890 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.166%

Overall 0.0118% 190/1,613,658 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.214%	468
South Asian	0.0681%	1,469
Remaining individualsnot grpmax-eligible	0.0384%	2,604
European (non-Finnish)	0.000678%	147,505

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.Ala331=
Coding: c.993C>T
MANE Select: NM_005173
dbSNP: rs183496663
Type: single nucleotide variant
Location: chr17:3947493 (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.Ala424= 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-ala331 (accessed [today's date]).

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