Is CDH23 p.Pro2523= (c.7569G>A) pathogenic?

CDH23 p.Pro2523= (c.7569G>A) is classified Likely benign in CDH23 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-16). Ultra-rare (popmax 0.0178%, eas); Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Pro2523= (c.7569G>A)?

CDH23 p.Pro2523= (c.7569G>A) is associated with Usher syndrome type 1 (ClinVar).

How common is CDH23 p.Pro2523= (c.7569G>A) in the general population?

CDH23 p.Pro2523= (c.7569G>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

How is Usher syndrome inherited?

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

CDH23 p.Pro2523=

c.7569G>A · rs533989797 · VCV752142

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

Usher syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -10	GERP -4
Overall
CADD	0.133	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,888 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00458% 74/1,614,016 alleles · ultra-rare exomes 65/1,461,700 · genomes 9/152,316 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,611
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00466%	21,453
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
African / African-American	0.00267%	37,520
South Asian	0.0022%	45,543

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.Pro2523=
Coding: c.7569G>A
MANE Select: NM_022124
dbSNP: rs533989797
Type: single nucleotide variant
Location: chr10:71802984 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2523: the cadherin 24 domain

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)

Similar variants

CDH23 p.Pro2523Leu Uncertain significance ★★ same residue
CDH23 p.Pro2523Ser 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.Arg301Gln 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-pro2523 (accessed [today's date]).

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