Is CDH23 p.Arg116fs (c.345_346del) pathogenic?

CDH23 p.Arg116fs (c.345346del) is classified Likely pathogenic in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). Very rare (popmax 0.00017%, nfe); Associated with pituitary adenoma 5, multiple types.

What condition is associated with CDH23 p.Arg116fs (c.345_346del)?

CDH23 p.Arg116fs (c.345_346del) is associated with pituitary adenoma 5, multiple types (ClinVar).

How common is CDH23 p.Arg116fs (c.345_346del) in the general population?

CDH23 p.Arg116fs (c.345_346del) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Familial isolated pituitary adenoma inherited?

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

CDH23 p.Arg116fs

c.345_346del · rs2493197193 · VCV2680474

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 6 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	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 0.00017% European (non-Finnish) · 2/1,179,460 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,136 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.Arg116fs
Coding: c.345_346del
MANE Select: NM_022124
dbSNP: rs2493197193
Type: Microsatellite
Location: chr10:71511125 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 116: the cadherin 1 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

For Familial isolated pituitary adenoma (Orphanet):

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

Similar variants

CDH23 p.Gln462fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Phe2664del Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ser3157fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Val2274fs Likely pathogenic ★★ same condition
CDH23 p.Arg116Gln Uncertain significance ★★ ⚠ same residue
CDH23 p.Arg116Gly Uncertain significance ★★ ⚠ same residue
CDH23 p.Arg116Trp Uncertain significance ★ ⚠ same residue
CDH23 p.Arg116= Likely benign ★ same residue

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-arg116fs (accessed [today's date]).

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