Is CDH23 p.Trp13Ter (c.39G>A) pathogenic?

CDH23 p.Trp13Ter (c.39G>A) is classified Likely pathogenic in CDH23 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-09). Absent from gnomAD v4.1; Associated with pituitary adenoma 5, multiple types.

What condition is associated with CDH23 p.Trp13Ter (c.39G>A)?

CDH23 p.Trp13Ter (c.39G>A) is associated with pituitary adenoma 5, multiple types, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

How common is CDH23 p.Trp13Ter (c.39G>A) in the general population?

CDH23 p.Trp13Ter (c.39G>A) is absent from gnomAD v4.1 (gnomAD).

How is Familial isolated pituitary adenoma inherited?

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

CDH23 p.Trp13Ter

c.39G>A · rs1325941288 · VCV3241049

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,575,256)

Conditions

pituitary adenoma 5, multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 70
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.1, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,575,256). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDH23
Protein: p.Trp13Ter
Coding: c.39G>A
MANE Select: NM_022124
dbSNP: rs1325941288
Type: single nucleotide variant
Location: chr10:71439870 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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: autosomal recessive nonsyndromic hearing loss 12

For Familial isolated pituitary adenoma (Orphanet):

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

Similar variants

CDH23 p.Trp13Cys Uncertain significance ★★ ⚠ same residue
CDH23 p.Trp13Leu Uncertain significance ★ ⚠ same residue
CDH23 p.Arg2029Trp Pathogenic ★★★ ⚠ same condition
CDH23 p.Asp127Gly Likely pathogenic ★★★ same condition
CDH23 p.Glu956Lys Pathogenic ★★★ same condition
CDH23 p.Pro240Leu Pathogenic ★★★ same condition
CDH23 c.1515-12G>A Uncertain significance ★★★ same condition
CDH23 p.Ala3190Val Uncertain significance ★★★ ⚠ 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-trp13ter (accessed [today's date]).

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