Is CASR p.Arg752= (c.2256C>A) pathogenic?

CASR p.Arg752= (c.2256C>A) is classified Likely benign in CASR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-13). Absent from gnomAD v4.1; Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with CASR p.Arg752= (c.2256C>A)?

CASR p.Arg752= (c.2256C>A) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is CASR p.Arg752= (c.2256C>A) in the general population?

CASR p.Arg752= (c.2256C>A) is absent from gnomAD v4.1 (gnomAD).

CASR p.Arg752=

c.2256C>A · rs77472303 · VCV1788527

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Nephrolithiasis/nephrocalcinosis

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 0.91	GERP -0.85, phastCons 1
Overall
CADD	7.759	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CASR
Protein: p.Arg752=
Coding: c.2256C>A
MANE Select: NM_000388
dbSNP: rs77472303
Type: single nucleotide variant
Location: chr3:122284210 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 752: a UniProt-annotated variant site (in hhc1; impaired homodimerization; impaired cell membrane localization); a β-strand

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

Disease context

Nephrolithiasis/nephrocalcinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASR p.Arg752His Conflicting classifications of pathogenicity ★ ⚠ same residue
CASR p.Arg752Gly Uncertain significance ★★ ⚠ same residue
CASR p.Arg752Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CASR p.Arg752Pro Uncertain significance ★ ⚠ same residue
CASR p.Arg752Ser Uncertain significance ★ ⚠ same residue
CASR p.Arg465Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CASR p.Glu767Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CASR p.Ile555Thr Pathogenic/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-arg752 (accessed [today's date]).

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