Is ATP2A2 p.Leu796Pro (c.2387T>C) pathogenic?

ATP2A2 p.Leu796Pro (c.2387T>C) is classified Uncertain significance in ATP2A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-01). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1.

How common is ATP2A2 p.Leu796Pro (c.2387T>C) in the general population?

ATP2A2 p.Leu796Pro (c.2387T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATP2A2 p.Leu796Pro (c.2387T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

ATP2A2 p.Leu796Pro

c.2387T>C · rs1592864875 · VCV806941

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 4% in ATP2A2
REVEL	0.974	strongly pathogenic-leaning
SaProt	LLR -16.43	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 2,423 bp · p 1.4e-21 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATP2A2
Protein: p.Leu796Pro
Coding: c.2387T>C
MANE Select: NM_170665
dbSNP: rs1592864875
Type: single nucleotide variant
Location: chr12:110343300 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.46 · 15 PDB
Residue 796: an α-helix; the 'interaction with pln' region; the 'interaction with tmem64 and pdia3' region; a UniProt-annotated variant site (in dd)

Full ATP2A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP2A2 p.Ala803Thr Pathogenic/Likely pathogenic ★★ same type
ATP2A2 p.Asn767Ser Pathogenic/Likely pathogenic ★★ same type
ATP2A2 p.Asp702Asn Pathogenic ★★ same type
ATP2A2 p.Gly211Asp Pathogenic ★★ same type
ATP2A2 p.Ile348Thr Pathogenic/Likely pathogenic ★★ same type
ATP2A2 p.Met1Leu Pathogenic ★★ same type
ATP2A2 p.Met1Val Pathogenic ★★ same type
ATP2A2 p.Pro602Leu Pathogenic ★★ same type

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/atp2a2-p-leu796pro (accessed [today's date]).

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