Is CASR p.Arg185= (c.553C>A) pathogenic?

CASR p.Arg185= (c.553C>A) is classified Likely benign in CASR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-07-10). Very rare (popmax 0.00833%, amr); Associated with familial hypocalciuric hypercalcemia.

What condition is associated with CASR p.Arg185= (c.553C>A)?

CASR p.Arg185= (c.553C>A) is associated with familial hypocalciuric hypercalcemia, autosomal dominant hypocalcemia 1 (ClinVar).

How common is CASR p.Arg185= (c.553C>A) in the general population?

CASR p.Arg185= (c.553C>A) is very rare (popmax 0.00833%, amr) (gnomAD).

How is Familial hypocalciuric hypercalcemia inherited?

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

CASR p.Arg185=

c.553C>A · rs104893707 · VCV532592

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

familial hypocalciuric hypercalcemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Overall
CADD	12.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,004 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000991% 16/1,614,058 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,001
European (non-Finnish)	0.000932%	107,274

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CASR
Protein: p.Arg185=
Coding: c.553C>A
MANE Select: NM_000388
dbSNP: rs104893707
Type: single nucleotide variant
Location: chr3:122261588 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 185: a UniProt-annotated variant site (in hhc1; decreased g protein-coupled receptor signaling pathway); 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

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.Arg185Gln Pathogenic ★★ same residue
CASR p.Arg185Ter Pathogenic ★★ same residue
CASR p.Arg185Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CASR p.Arg185fs Pathogenic/Likely pathogenic ★★ same residue
CASR p.Arg185Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
CASR c.1378-1G>C Likely pathogenic ★★ same condition
CASR c.1608+1G>A Likely pathogenic ★★ same condition
CASR c.1609-2A>G 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/casr-p-arg185 (accessed [today's date]).

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