Is ATP2B2 p.Phe123fs (c.367_368del) pathogenic?

ATP2B2 p.Phe123fs (c.367368del) is classified Likely pathogenic in ATP2B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). Associated with hearing loss, autosomal dominant 82.

What condition is associated with ATP2B2 p.Phe123fs (c.367_368del)?

ATP2B2 p.Phe123fs (c.367_368del) is associated with hearing loss, autosomal dominant 82 (ClinVar).

ATP2B2 p.Phe123fs

c.367_368del · VCV4852248

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hearing loss, autosomal dominant 82

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 3 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.5	GERP 0.76, phastCons 1

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

Variant & gene context

Gene: ATP2B2
Protein: p.Phe123fs
Coding: c.367_368del
MANE Select: NM_001001331
Type: Deletion
Location: chr3:10410647 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.83

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

Disease context

hearing loss, autosomal dominant 82 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATP2B2 p.Arg482fs Pathogenic ★ same condition
ATP2B2 p.Leu121fs Likely pathogenic ★ same condition
ATP2B2 p.Ala319fs Pathogenic same condition
ATP2B2 p.Glu457Lys Likely pathogenic ★★ same condition
ATP2B2 p.Arg1142His Uncertain significance ★★ ⚠ same condition
ATP2B2 p.Asp779Gly Uncertain significance ★★ ⚠ same condition
ATP2B2 c.1043-2A>G Pathogenic ★ same condition
ATP2B2 p.Asp316fs Likely pathogenic ★ 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/atp2b2-p-phe123fs (accessed [today's date]).

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