Is ATP2B2 p.Asp707Glu (c.2121C>A) pathogenic?

ATP2B2 p.Asp707Glu (c.2121C>A) is classified Likely pathogenic in ATP2B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-03). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1.

How common is ATP2B2 p.Asp707Glu (c.2121C>A) in the general population?

ATP2B2 p.Asp707Glu (c.2121C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATP2B2 p.Asp707Glu (c.2121C>A)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

ATP2B2 p.Asp707Glu

c.2121C>A · VCV3456781

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic ✓ concordant with ClinVar · top 5% in ATP2B2
REVEL	0.873	moderately pathogenic-leaning
SaProt	LLR -13.93	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 3.9	GERP 0.35, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 28 kb · p 6e-17 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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: ATP2B2
Protein: p.Asp707Glu
Coding: c.2121C>A
MANE Select: NM_001001331
Type: single nucleotide variant
Location: chr3:10358706 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.83
Residue 707: a UniProt-annotated variant site (in dfna82)

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

Similar variants

ATP2B2 c.2136+1G>A Pathogenic/Likely pathogenic ★★ same type
ATP2B2 p.Arg1132Ter Pathogenic/Likely pathogenic ★★ same type
ATP2B2 p.Glu457Lys Likely pathogenic ★★ same type
ATP2B2 p.Gly821Arg Pathogenic ★★ same type
ATP2B2 p.Thr503Met Pathogenic/Likely pathogenic ★★ same type
ATP2B2 c.2316+5G>A Uncertain significance ★★ same type
ATP2B2 c.3420+1998G>T Uncertain significance ★★ same type
ATP2B2 p.Ala135Val Uncertain significance ★★ ⚠ 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-asp707glu (accessed [today's date]).

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