Is CDH23 p.Asn1305= (c.3915C>T) pathogenic?

CDH23 p.Asn1305= (c.3915C>T) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-12). Very rare (popmax 0.00549%, sas); Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Asn1305= (c.3915C>T)?

CDH23 p.Asn1305= (c.3915C>T) is associated with autosomal recessive nonsyndromic hearing loss 12, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Asn1305= (c.3915C>T) in the general population?

CDH23 p.Asn1305= (c.3915C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

CDH23 p.Asn1305=

c.3915C>T · rs568924674 · VCV300427

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

autosomal recessive nonsyndromic hearing loss 12

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 -15	GERP -5.5
Overall
CADD	0.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,060 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00322% 52/1,613,784 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,212
Admixed American	0.005%	19,997
African / African-American	0.004%	24,978
European (non-Finnish)	0.00339%	29,496
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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.Asn1305=
Coding: c.3915C>T
MANE Select: NM_001164375 · reported on NM_022124
dbSNP: rs568924674
Type: single nucleotide variant
Location: chr10:71732186 (GRCh38)

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

Disease context

autosomal recessive nonsyndromic hearing loss 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1D

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-asn1305 (accessed [today's date]).

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