Is CASR p.Glu519fs (c.1557_1560del) pathogenic?

CASR p.Glu519fs (c.15571560del) is classified Pathogenic in CASR (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-08). Absent from gnomAD; Associated with familial hypocalciuric hypercalcemia.

What condition is associated with CASR p.Glu519fs (c.1557_1560del)?

CASR p.Glu519fs (c.1557_1560del) is associated with familial hypocalciuric hypercalcemia, autosomal dominant hypocalcemia 1 (ClinVar).

How common is CASR p.Glu519fs (c.1557_1560del) in the general population?

CASR p.Glu519fs (c.1557_1560del) is absent from gnomAD (gnomAD).

How is Familial hypocalciuric hypercalcemia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CASR p.Glu519fs

c.1557_1560del · rs2107643705 · VCV1376400

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

familial hypocalciuric hypercalcemia

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 5 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	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.Glu519fs
Coding: c.1557_1560del
MANE Select: NM_000388
dbSNP: rs2107643705
Type: Deletion
Location: chr3:122275988 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 519: a β-strand; a disulfide bond

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

Disease context

familial hypocalciuric hypercalcemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant hypocalcemia 1

For Familial hypocalciuric hypercalcemia (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

CASR p.Glu519= 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-glu519fs (accessed [today's date]).

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