Is CDH23 p.Pro1163fs (c.3486dup) pathogenic?

CDH23 p.Pro1163fs (c.3486dup) is classified Likely pathogenic in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-25). Very rare (popmax 0.00017%, nfe); Associated with pituitary adenoma 5, multiple types.

What condition is associated with CDH23 p.Pro1163fs (c.3486dup)?

CDH23 p.Pro1163fs (c.3486dup) is associated with pituitary adenoma 5, multiple types (ClinVar).

How common is CDH23 p.Pro1163fs (c.3486dup) in the general population?

CDH23 p.Pro1163fs (c.3486dup) 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.Pro1163fs

c.3486dup · rs2494152459 · VCV2680476

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.44	GERP -0.66, phastCons 0.69

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) · 2/1,179,900 alleles

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

Overall 0.000137% 2/1,461,702 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.Pro1163fs
Coding: c.3486dup
MANE Select: NM_001164375 · reported on NM_022124
dbSNP: rs2494152459
Type: Duplication
Location: chr10:71725424 (GRCh38)

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

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-pro1163fs (accessed [today's date]).

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