Is CDH23 p.Ser395Pro (c.1183T>C) pathogenic?

CDH23 p.Ser395Pro (c.1183T>C) is classified Uncertain significance in CDH23 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely pathogenic (0.8935); Absent from gnomAD v4.1; Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Ser395Pro (c.1183T>C)?

CDH23 p.Ser395Pro (c.1183T>C) is associated with Usher syndrome type 1 (ClinVar).

How common is CDH23 p.Ser395Pro (c.1183T>C) in the general population?

CDH23 p.Ser395Pro (c.1183T>C) is absent from gnomAD v4.1 (gnomAD).

How is Usher syndrome inherited?

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

What do computational predictors say about CDH23 p.Ser395Pro (c.1183T>C)?

AlphaMissense predicts likely pathogenic (score 0.8935) — an in-silico prediction, not a clinical call.

CDH23 p.Ser395Pro

c.1183T>C · VCV4064057

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8935 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.8935	likely pathogenic
REVEL	0.444	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDH23
Protein: p.Ser395Pro
Coding: c.1183T>C
MANE Select: NM_022124
Type: single nucleotide variant
Location: chr10:71645873 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 395: the cadherin 4 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.Ser395= Conflicting classifications of pathogenicity ★ same residue
CDH23 p.Ser395Cys 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-ser395pro (accessed [today's date]).

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