Is CDH23 p.Val363= (c.1089C>T) pathogenic?

CDH23 p.Val363= (c.1089C>T) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.03%, sas); Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Val363= (c.1089C>T)?

CDH23 p.Val363= (c.1089C>T) is associated with autosomal recessive nonsyndromic hearing loss 12, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Val363= (c.1089C>T) in the general population?

CDH23 p.Val363= (c.1089C>T) is low-frequency (popmax 1.03%, sas) (gnomAD).

CDH23 p.Val363=

c.1089C>T · rs556135873 · VCV179109

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.03%, sas)

Conditions

autosomal recessive nonsyndromic hearing loss 12

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.94 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.1	GERP -3.5
Overall
CADD	5.355	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.03% South Asian · 941/91,062 alleles

Filtering AF 0.979% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.957%

Overall 0.0626% 1,011/1,613,910 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.03%	97
Remaining individualsnot grpmax-eligible	0.0832%	1,202
Middle Eastern	0.033%	3,031
East Asian	0.00223%	44,886
African / African-American	0.00133%	75,028
European (non-Finnish)	0.00119%	84,277

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.Val363=
Coding: c.1089C>T
MANE Select: NM_022124
dbSNP: rs556135873
Type: single nucleotide variant
Location: chr10:71617348 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 363: the cadherin 4 domain

Full CDH23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive nonsyndromic hearing loss 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1D

Similar variants

CDH23 p.Val363fs Pathogenic/Likely pathogenic ★★ 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-val363 (accessed [today's date]).

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