Is CDH23 p.Arg2489= (c.7467C>T) pathogenic?

CDH23 p.Arg2489= (c.7467C>T) is classified Benign/Likely benign in CDH23 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Common (popmax 7.39%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 1D.

What condition is associated with CDH23 p.Arg2489= (c.7467C>T)?

CDH23 p.Arg2489= (c.7467C>T) is associated with Usher syndrome type 1D, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

CDH23 p.Arg2489=

Q: How common is CDH23 p.Arg2489= (c.7467C>T) in the general population?

CDH23 p.Arg2489= (c.7467C>T) is common (popmax 7.39%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7467C>T · rs111033289 · VCV46031

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 7.39%, eas) — 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 -0.015	GERP -3.4, phastCons 0.021
Overall
CADD	7.216	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.39% East Asian · 3,318/44,872 alleles

Filtering AF 7.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1%

Overall 0.593% 9,568/1,613,816 alleles · common exomes 6,877/1,461,606 · genomes 2,691/152,210 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	7.39%	14
African / African-American	4.31%	23
Admixed American	1.39%	72
Remaining individualsnot grpmax-eligible	1.01%	99
South Asian	0.593%	169
Ashkenazi Jewishnot grpmax-eligible	0.388%	257
Finnishnot grpmax-eligible	0.373%	268
Middle Eastern	0.314%	319
European (non-Finnish)	0.0542%	1,843

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.Arg2489=
Coding: c.7467C>T
MANE Select: NM_022124
dbSNP: rs111033289
Type: single nucleotide variant
Location: chr10:71800740 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2489: a UniProt-annotated variant site (in); the cadherin 23 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.Arg2489His Uncertain significance ★★ ⚠ same residue
CDH23 p.Arg2489Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH23 p.Arg2489Gly 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

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-arg2489 (accessed [today's date]).

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