Is CASR p.Lys897Arg (c.2690A>G) pathogenic?

CASR p.Lys897Arg (c.2690A>G) is classified Uncertain significance in CASR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: likely benign (0.073); Very rare (popmax 8.48e-05%, nfe); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with CASR p.Lys897Arg (c.2690A>G)?

CASR p.Lys897Arg (c.2690A>G) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is CASR p.Lys897Arg (c.2690A>G) in the general population?

CASR p.Lys897Arg (c.2690A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CASR p.Lys897Arg (c.2690A>G)?

AlphaMissense predicts likely benign (score 0.073) — an in-silico prediction, not a clinical call.

CASR p.Lys897Arg

c.2690A>G · rs897282559 · VCV821677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.073 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
AlphaMissense	0.073	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -5.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 554 bp · p 0.066 · regional, not allelic
Overall
CADD	18.68	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,930 alleles

Overall 6.84e-05% 1/1,461,648 alleles · very rare

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.Lys897Arg
Coding: c.2690A>G
MANE Select: NM_000388
dbSNP: rs897282559
Type: single nucleotide variant
Location: chr3:122284644 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 897: a UniProt-annotated variant site (in hhc1; impaired homodimerization; impaired cell membrane localization); the 'c-terminus' region; the 'interaction with rnf19a' region; the 'arginine-rich retention motif' region; the 'disordered' region

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.Arg465Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CASR p.Glu767Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CASR p.Ile555Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CASR p.Ala168Ser Uncertain significance ★★ ⚠ same condition
CASR p.Ala390Asp Uncertain significance ★★ ⚠ same condition
CASR p.Ala430Ser Uncertain significance ★★ ⚠ same condition
CASR p.Ala45Glu Uncertain significance ★★ ⚠ same condition
CASR p.Ala600Asp 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-lys897arg (accessed [today's date]).

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