Is ATP2B2 p.Glu684fs (c.2048dup) pathogenic?

ATP2B2 p.Glu684fs (c.2048dup) is classified Likely pathogenic in ATP2B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-01). Absent from gnomAD.

How common is ATP2B2 p.Glu684fs (c.2048dup) in the general population?

ATP2B2 p.Glu684fs (c.2048dup) is absent from gnomAD (gnomAD).

ATP2B2 p.Glu684fs

c.2048dup · rs1575005369 · VCV809421

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 14 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -10	GERP -5.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATP2B2
Protein: p.Glu684fs
Coding: c.2048dup
MANE Select: NM_001001331
dbSNP: rs1575005369
Type: Duplication
Location: chr3:10358778 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.83
Residue 684: a UniProt-annotated variant site (in dfna82)

Full ATP2B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP2B2 p.Ala642fs Pathogenic ★ same type
ATP2B2 p.Arg1020fs Pathogenic ★ same type
ATP2B2 p.Arg588fs Pathogenic ★ same type
ATP2B2 p.Asp316fs Likely pathogenic ★ same type
ATP2B2 p.Ile186fs Likely pathogenic ★ same type
ATP2B2 p.Ile839_Ala840insIle Likely pathogenic ★ same type
ATP2B2 p.Leu459fs Likely pathogenic ★ same type
ATP2B2 p.Met910fs 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/atp2b2-p-glu684fs (accessed [today's date]).

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