Is CASR p.Pro682fs (c.2045del) pathogenic?

CASR p.Pro682fs (c.2045del) is classified Pathogenic in CASR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). Absent from gnomAD; Associated with autosomal dominant hypocalcemia 1.

What condition is associated with CASR p.Pro682fs (c.2045del)?

CASR p.Pro682fs (c.2045del) is associated with autosomal dominant hypocalcemia 1, familial hypocalciuric hypercalcemia (ClinVar).

How common is CASR p.Pro682fs (c.2045del) in the general population?

CASR p.Pro682fs (c.2045del) is absent from gnomAD (gnomAD).

CASR p.Pro682fs

c.2045del · rs2473277634 · VCV2003725

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	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 0.26, 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.Pro682fs
Coding: c.2045del
MANE Select: NM_000388
dbSNP: rs2473277634
Type: Deletion
Location: chr3:122283998 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 682: a UniProt-annotated variant site (in hhc1; impaired homodimerization; impaired cell membrane localization); an α-helix

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.Pro682= Likely benign ★★ same residue
CASR p.Pro682Leu 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-pro682fs (accessed [today's date]).

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