Is CASR p.Val513fs (c.1536_1537del) pathogenic?

CASR p.Val513fs (c.15361537del) is classified Likely pathogenic in CASR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-21). Associated with CASR-related disorder.

What condition is associated with CASR p.Val513fs (c.1536_1537del)?

CASR p.Val513fs (c.1536_1537del) is associated with CASR-related disorder (ClinVar).

CASR p.Val513fs

c.1536_1537del · VCV4963839

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

CASR-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 5 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CASR
Protein: p.Val513fs
Coding: c.1536_1537del
MANE Select: NM_000388
Type: Deletion
Location: chr3:122275970 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 513: a β-strand; a disulfide bond

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

Disease context

CASR-related disorder

Similar variants

CASR p.Val513Ile Uncertain significance ★★ ⚠ same residue
CASR p.Val513= Likely benign ★★ same residue
CASR p.Ala826fs Likely pathogenic ★ same condition
CASR p.Cys765fs Likely pathogenic ★ same condition
CASR p.Val9fs Pathogenic ★ same condition
CASR p.Arg220Trp Pathogenic/Likely pathogenic ★★ same condition
CASR p.Arg227Ter Pathogenic/Likely pathogenic ★★ same condition
CASR p.Arg392Ter 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-val513fs (accessed [today's date]).

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