Is CDH23 p.Asp1365= (c.4095C>T) pathogenic?

CDH23 p.Asp1365= (c.4095C>T) is classified Likely benign in CDH23 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-01). Ultra-rare (popmax 0.0942%, amr); Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Asp1365= (c.4095C>T)?

CDH23 p.Asp1365= (c.4095C>T) is associated with Usher syndrome type 1 (ClinVar).

How common is CDH23 p.Asp1365= (c.4095C>T) in the general population?

CDH23 p.Asp1365= (c.4095C>T) is ultra-rare (popmax 0.0942%, amr) (gnomAD).

How is Usher syndrome inherited?

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

CDH23 p.Asp1365=

c.4095C>T · rs368582818 · VCV730126

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0942%, amr)

Conditions

Usher syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.7	GERP -5.4
Overall
CADD	5.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0942% Admixed American · 49/51,990 alleles

Filtering AF 0.0732% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0657%

Overall 0.00953% 149/1,563,320 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0942%	1,061
African / African-American	0.0503%	1,989
Remaining individualsnot grpmax-eligible	0.0247%	4,048
East Asian	0.0072%	13,887
European (non-Finnish)	0.00381%	26,214
Finnishnot grpmax-eligible	0.00164%	60,854

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.Asp1365=
Coding: c.4095C>T
MANE Select: NM_001164375 · reported on NM_022124
dbSNP: rs368582818
Type: single nucleotide variant
Location: chr10:71732366 (GRCh38)

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

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

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-asp1365 (accessed [today's date]).

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