Is CASR p.Pro559= (c.1677C>T) pathogenic?

CASR p.Pro559= (c.1677C>T) is classified Likely benign in CASR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-26). Absent from gnomAD v4.1; Associated with autosomal dominant hypocalcemia 1.

What condition is associated with CASR p.Pro559= (c.1677C>T)?

CASR p.Pro559= (c.1677C>T) is associated with autosomal dominant hypocalcemia 1, familial hypocalciuric hypercalcemia (ClinVar).

How common is CASR p.Pro559= (c.1677C>T) in the general population?

CASR p.Pro559= (c.1677C>T) is absent from gnomAD v4.1 (gnomAD).

CASR p.Pro559=

c.1677C>T · rs2074898411 · VCV2933758

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal dominant hypocalcemia 1

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 -0.028	GERP -1.5, phastCons 0.72
Overall
CADD	9.26	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.Pro559=
Coding: c.1677C>T
MANE Select: NM_000388
dbSNP: rs2074898411
Type: single nucleotide variant
Location: chr3:122282181 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 559: the 'cysteine-rich (cr)' region; a disulfide bond

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

Disease context

autosomal dominant hypocalcemia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypocalciuric hypercalcemia

Similar variants

CASR p.Pro559His Likely pathogenic ★ ⚠ same residue
CASR p.Pro559Thr Conflicting classifications of pathogenicity ★ ⚠ 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-pro559 (accessed [today's date]).

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