Is CASR p.Ile33fs (c.97_98del) pathogenic?

CASR p.Ile33fs (c.9798del) is classified Pathogenic in CASR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-17). Absent from gnomAD; Associated with autosomal dominant hypocalcemia 1.

What condition is associated with CASR p.Ile33fs (c.97_98del)?

CASR p.Ile33fs (c.97_98del) is associated with autosomal dominant hypocalcemia 1, familial hypocalciuric hypercalcemia (ClinVar).

How common is CASR p.Ile33fs (c.97_98del) in the general population?

CASR p.Ile33fs (c.97_98del) is absent from gnomAD (gnomAD).

CASR p.Ile33fs

c.97_98del · rs2473205414 · VCV2943313

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 2 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 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: CASR
Protein: p.Ile33fs
Coding: c.97_98del
MANE Select: NM_000388
dbSNP: rs2473205414
Type: Deletion
Location: chr3:122254285 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 33: the 'ligand-binding 1 (lb1)' region; a β-strand

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.Ile33= Likely benign ★★ same residue
CASR p.Ile33Ser Conflicting classifications of pathogenicity ★ ⚠ 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

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-ile33fs (accessed [today's date]).

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