Is CDH23 p.Ser384Arg (c.1152C>A) pathogenic?

CDH23 p.Ser384Arg (c.1152C>A) is classified Pathogenic/Likely pathogenic in CDH23 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2024-06-27). AlphaMissense: likely pathogenic (0.9229); Ultra-rare (popmax 0.0165%, mid); Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Ser384Arg (c.1152C>A)?

CDH23 p.Ser384Arg (c.1152C>A) is associated with Usher syndrome type 1, Usher syndrome type 1D, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

How common is CDH23 p.Ser384Arg (c.1152C>A) in the general population?

CDH23 p.Ser384Arg (c.1152C>A) is ultra-rare (popmax 0.0165%, mid) (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.Ser384Arg (c.1152C>A)?

AlphaMissense predicts likely pathogenic (score 0.9229) — an in-silico prediction, not a clinical call.

CDH23 p.Ser384Arg

c.1152C>A · rs2493815701 · VCV2501245

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9229 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.9229	likely pathogenic ✓ concordant with ClinVar
REVEL	0.342	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.32, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	25.3	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

Grpmax group 0.0165% Middle Eastern · 1/6,046 alleles

Overall 0.000137% 2/1,458,508 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,046
European (non-Finnish)	8.49e-05%	1,177,406

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.Ser384Arg
Coding: c.1152C>A
MANE Select: NM_022124
dbSNP: rs2493815701
Type: single nucleotide variant
Location: chr10:71645842 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 384: 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

Also linked: Usher syndrome type 1D autosomal recessive nonsyndromic hearing loss 12 Usher syndrome pituitary adenoma 5, multiple types

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

CDH23 p.Ser384= Likely benign ★ 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.Ala3190Val 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-ser384arg (accessed [today's date]).

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