Is CDH23 p.Pro2523Ser (c.7567C>T) pathogenic?

CDH23 p.Pro2523Ser (c.7567C>T) is classified Uncertain significance in CDH23 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-12). AlphaMissense: likely benign (0.3132); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDH23 p.Pro2523Ser (c.7567C>T)?

CDH23 p.Pro2523Ser (c.7567C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDH23 p.Pro2523Ser (c.7567C>T) in the general population?

CDH23 p.Pro2523Ser (c.7567C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CDH23 p.Pro2523Ser (c.7567C>T)?

AlphaMissense predicts likely benign (score 0.3132) — an in-silico prediction, not a clinical call.

CDH23 p.Pro2523Ser

c.7567C>T · rs752326120 · VCV2148574

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3132 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3132	likely benign
REVEL	0.204	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 4,473 bp · p 9.3e-05 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,878 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,988 alleles · very rare exomes 8/1,461,708 · genomes 0/152,280 · joint denominator

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.Pro2523Ser
Coding: c.7567C>T
MANE Select: NM_022124
dbSNP: rs752326120
Type: single nucleotide variant
Location: chr10:71802982 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH23 p.Pro2523Leu Uncertain significance ★★ same residue
CDH23 p.Pro2523= Likely benign ★★ same residue
CDH23 p.Pro2523fs Likely pathogenic ★★ same residue
CDH23 p.Ala129Thr Uncertain significance ★★ ⚠ same condition
CDH23 p.Ala1464Glu Uncertain significance ★★ ⚠ same condition
CDH23 p.Ala1482Val Uncertain significance ★★ ⚠ same condition
CDH23 p.Ala1673Val Uncertain significance ★★ same condition
CDH23 p.Ala1878Thr 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-pro2523ser (accessed [today's date]).

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