Is CASR p.Glu277= (c.831G>A) pathogenic?

CASR p.Glu277= (c.831G>A) is classified Likely benign in CASR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-15). Absent from gnomAD v4.1; Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with CASR p.Glu277= (c.831G>A)?

CASR p.Glu277= (c.831G>A) is associated with Nephrolithiasis/nephrocalcinosis, autosomal dominant hypocalcemia 1, familial hypocalciuric hypercalcemia (ClinVar).

How common is CASR p.Glu277= (c.831G>A) in the general population?

CASR p.Glu277= (c.831G>A) is absent from gnomAD v4.1 (gnomAD).

CASR p.Glu277=

c.831G>A · rs2107632344 · VCV1149716

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 0.18	GERP -4.2, phastCons 0.14
Overall
CADD	3.215	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.Glu277=
Coding: c.831G>A
MANE Select: NM_000388
dbSNP: rs2107632344
Type: single nucleotide variant
Location: chr3:122261866 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 277: the 'ligand-binding 2 (lb2)' region; an α-helix; a disulfide bond

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

Also linked: autosomal dominant hypocalcemia 1 familial hypocalciuric hypercalcemia

Similar variants

CASR p.Glu277Asp Uncertain significance ★ ⚠ same residue
CASR p.Glu277Gln 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
CASR p.Ala581Val 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-glu277 (accessed [today's date]).

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