Is ATP2A3 p.His5= (c.15T>C) pathogenic?

ATP2A3 p.His5= (c.15T>C) is classified Benign in ATP2A3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-31). Common (popmax 47.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ATP2A3-related disorder.

What condition is associated with ATP2A3 p.His5= (c.15T>C)?

ATP2A3 p.His5= (c.15T>C) is associated with ATP2A3-related disorder (ClinVar).

ATP2A3 p.His5=

Q: How common is ATP2A3 p.His5= (c.15T>C) in the general population?

ATP2A3 p.His5= (c.15T>C) is common (popmax 47.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.15T>C · rs887384 · VCV3059913

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 47.8%, afr) — too common for a highly-penetrant pathogenic allele

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 6.1	GERP 0.082, phastCons 1
Overall
CADD	14.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47.8% African / African-American · 29,775/62,264 alleles

Filtering AF 47.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.2%

Overall 20.8% 263,357/1,269,010 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	47.8%	2
Amishnot grpmax-eligible	35.4%	3
Admixed American	30.2%	3
East Asian	26.2%	4
Middle Eastern	23%	4
Ashkenazi Jewishnot grpmax-eligible	21.8%	5
Remaining individualsnot grpmax-eligible	21%	5
European (non-Finnish)	19%	5
Finnishnot grpmax-eligible	16.8%	6
South Asian	15.9%	6

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.His5=
Coding: c.15T>C
MANE Select: NM_005173
dbSNP: rs887384
Type: single nucleotide variant
Location: chr17:3964277 (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-his5 (accessed [today's date]).

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