Is CDH23 p.Ser2182= (c.6546C>T) pathogenic?

CDH23 p.Ser2182= (c.6546C>T) is classified Likely benign in CDH23 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-21). Ultra-rare (popmax 0.0165%, mid); Associated with hearing loss disorder.

What condition is associated with CDH23 p.Ser2182= (c.6546C>T)?

CDH23 p.Ser2182= (c.6546C>T) is associated with hearing loss disorder (ClinVar).

How common is CDH23 p.Ser2182= (c.6546C>T) in the general population?

CDH23 p.Ser2182= (c.6546C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CDH23 p.Ser2182=

c.6546C>T · rs749008207 · VCV1064950

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

hearing loss disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.4	GERP -3.2
Overall
CADD	1.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000547% 8/1,461,702 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Finnishnot grpmax-eligible	0.00312%	32,005
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	75,042
European (non-Finnish)	0.000254%	393,298

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.Ser2182=
Coding: c.6546C>T
MANE Select: NM_022124
dbSNP: rs749008207
Type: single nucleotide variant
Location: chr10:71793474 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2182: the cadherin 21 domain

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

Disease context

hearing loss disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH23 p.Ser2182Arg Uncertain significance ★ ⚠ same residue
CDH23 p.Ser2182Asn Uncertain significance ★ ⚠ same residue
CDH23 p.Ala3190Val Uncertain significance ★★★ ⚠ same condition
CDH23 p.Ala1072Asp Likely pathogenic ★★ same condition
CDH23 p.Arg2845His Uncertain significance ★★ ⚠ same condition
CDH23 p.Arg3310Cys Uncertain significance ★★ ⚠ same condition
CDH23 p.Arg720Gln Uncertain significance ★★ same condition
CDH23 p.Leu2327His 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-ser2182 (accessed [today's date]).

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