Is CASR p.Phe656= (c.1968C>T) pathogenic?

CASR p.Phe656= (c.1968C>T) is classified Likely benign in CASR (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-10). Absent from gnomAD v4.1; Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with CASR p.Phe656= (c.1968C>T)?

CASR p.Phe656= (c.1968C>T) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is CASR p.Phe656= (c.1968C>T) in the general population?

CASR p.Phe656= (c.1968C>T) is absent from gnomAD v4.1 (gnomAD).

CASR p.Phe656=

c.1968C>T · rs2074926557 · VCV1783554

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 3.1	GERP 1.2, phastCons 1
Overall
CADD	11.57	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.Phe656=
Coding: c.1968C>T
MANE Select: NM_000388
dbSNP: rs2074926557
Type: single nucleotide variant
Location: chr3:122283922 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 656: a UniProt-annotated variant site (in hhc1; impaired homodimerization; impaired cell membrane localization); an α-helix

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.Phe656Leu 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
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

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-phe656 (accessed [today's date]).

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