Is CASR p.Ser182= (c.546T>A) pathogenic?

CASR p.Ser182= (c.546T>A) is classified Benign/Likely benign in CASR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-01). Ultra-rare (popmax 0.0613%, afr); Associated with familial hypocalciuric hypercalcemia.

What condition is associated with CASR p.Ser182= (c.546T>A)?

CASR p.Ser182= (c.546T>A) is associated with familial hypocalciuric hypercalcemia, autosomal dominant hypocalcemia 1 (ClinVar).

How common is CASR p.Ser182= (c.546T>A) in the general population?

CASR p.Ser182= (c.546T>A) is ultra-rare (popmax 0.0613%, afr) (gnomAD).

How is Familial hypocalciuric hypercalcemia inherited?

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

CASR p.Ser182=

c.546T>A · rs200545177 · VCV257609

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0613%, afr)

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 0.12	GERP -0.78, phastCons 0.93
Overall
CADD	8.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0613% African / African-American · 46/75,048 alleles

Filtering AF 0.0471% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0422%

Overall 0.00328% 53/1,614,204 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0613%	1,631
Remaining individualsnot grpmax-eligible	0.0064%	15,628
Admixed American	0.00333%	30,009
European (non-Finnish)	8.47e-05%	1,180,036

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.Ser182=
Coding: c.546T>A
MANE Select: NM_000388
dbSNP: rs200545177
Type: single nucleotide variant
Location: chr3:122261581 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 182: the 'ligand-binding 1 (lb1)' region

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.Ser182Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CASR p.Ser182Phe Uncertain significance ★ ⚠ same residue
CASR p.Ser182Tyr Uncertain significance ★ ⚠ 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
CASR c.186-1G>T Pathogenic ★★ same condition
CASR c.493-2A>C 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-ser182 (accessed [today's date]).

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