Is CASR p.Arg96fs (c.286del) pathogenic?

CASR p.Arg96fs (c.286del) is classified Pathogenic in CASR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). Associated with autosomal dominant hypocalcemia 1.

What condition is associated with CASR p.Arg96fs (c.286del)?

CASR p.Arg96fs (c.286del) is associated with autosomal dominant hypocalcemia 1, familial hypocalciuric hypercalcemia (ClinVar).

CASR p.Arg96fs

c.286del · VCV4791916

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal dominant hypocalcemia 1

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 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP 1.2, phastCons 1

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

Variant & gene context

Gene: CASR
Protein: p.Arg96fs
Coding: c.286del
MANE Select: NM_000388
Type: Deletion
Location: chr3:122257181 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 96: the 'ligand-binding 1 (lb1)' region; a β-strand; a disulfide bond

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

Disease context

autosomal dominant hypocalcemia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypocalciuric hypercalcemia

Similar variants

CASR p.Arg96= Likely benign ★★ same residue
CASR p.Arg185fs Pathogenic/Likely pathogenic ★★ same condition
CASR p.Glu56fs Pathogenic ★★ same condition
CASR p.Gly623fs Pathogenic ★★ same condition
CASR p.Ile223fs Pathogenic/Likely pathogenic ★★ same condition
CASR p.Phe183fs Pathogenic ★★ same condition
CASR c.1608+5del Uncertain significance ★★ same condition
CASR p.Ala423del Uncertain significance ★★ 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/casr-p-arg96fs (accessed [today's date]).

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