Is CDH23 p.Arg2115fs (c.6344del) pathogenic?

CDH23 p.Arg2115fs (c.6344del) is classified Pathogenic/Likely pathogenic in CDH23 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-16). Very rare (popmax 0.0011%, sas); Associated with pituitary adenoma 5, multiple types.

What condition is associated with CDH23 p.Arg2115fs (c.6344del)?

CDH23 p.Arg2115fs (c.6344del) is associated with pituitary adenoma 5, multiple types, Usher syndrome type 1 (ClinVar).

How common is CDH23 p.Arg2115fs (c.6344del) in the general population?

CDH23 p.Arg2115fs (c.6344del) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Familial isolated pituitary adenoma inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CDH23 p.Arg2115fs

c.6344del · rs1589424694 · VCV654212

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

pituitary adenoma 5, multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 48 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,066 alleles

Overall 6.84e-05% 1/1,461,668 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: CDH23
Protein: p.Arg2115fs
Coding: c.6344del
MANE Select: NM_022124
dbSNP: rs1589424694
Type: Deletion
Location: chr10:71793272 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2115: a UniProt-annotated variant site (in pita5; uncertain significance); the cadherin 20 domain

Full CDH23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pituitary adenoma 5, multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1

For Familial isolated pituitary adenoma (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Elderly, Infancy

Similar variants

CDH23 p.Arg2115His Uncertain significance ★★ ⚠ same residue
CDH23 p.Arg2115Ser Uncertain significance ★ ⚠ same residue
CDH23 c.1143_1176del Pathogenic/Likely pathogenic ★★ same condition
CDH23 c.336+1del Likely pathogenic ★★ same condition
CDH23 c.9280_9286del Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ala2232_Val2233insTer Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ala2309fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ala2685fs 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/cdh23-p-arg2115fs (accessed [today's date]).

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