Is CDH23 p.Asp1447= (c.4341T>C) pathogenic?

CDH23 p.Asp1447= (c.4341T>C) is classified Benign in CDH23 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-06-19). Common (popmax 15.1%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 1D.

What condition is associated with CDH23 p.Asp1447= (c.4341T>C)?

CDH23 p.Asp1447= (c.4341T>C) is associated with Usher syndrome type 1D, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

CDH23 p.Asp1447=

Q: How common is CDH23 p.Asp1447= (c.4341T>C) in the general population?

CDH23 p.Asp1447= (c.4341T>C) is common (popmax 15.1%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4341T>C · rs12218564 · VCV45945

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 15.1%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

Usher syndrome type 1D

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7	GERP -5.7
Overall
CADD	0.625	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.1% Admixed American · 9,078/59,990 alleles

Filtering AF 14.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.8%

Overall 1.06% 17,143/1,613,346 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	15.1%	7
East Asian	12.8%	8
Remaining individualsnot grpmax-eligible	1.32%	76
Finnishnot grpmax-eligible	1.09%	92
Ashkenazi Jewishnot grpmax-eligible	0.389%	257
South Asian	0.248%	403
African / African-American	0.156%	641
Middle Eastern	0.066%	1,515
European (non-Finnish)	0.0285%	3,511

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.Asp1447=
Coding: c.4341T>C
MANE Select: NM_022124
dbSNP: rs12218564
Type: single nucleotide variant
Location: chr10:71738629 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1447: the cadherin 14 domain

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

Disease context

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

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 12

Similar variants

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
CDH23 p.Arg301Gln Uncertain significance ★★★ same condition
CDH23 p.Arg3189Gln 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-asp1447 (accessed [today's date]).

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