Is CDH23 p.Gly68= (c.204C>T) pathogenic?

CDH23 p.Gly68= (c.204C>T) is classified Benign/Likely benign in CDH23 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Low-frequency (popmax 4.15%, afr); Associated with Usher syndrome type 1D.

What condition is associated with CDH23 p.Gly68= (c.204C>T)?

CDH23 p.Gly68= (c.204C>T) is associated with Usher syndrome type 1D, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

How common is CDH23 p.Gly68= (c.204C>T) in the general population?

CDH23 p.Gly68= (c.204C>T) is low-frequency (popmax 4.15%, afr) (gnomAD).

CDH23 p.Gly68=

c.204C>T · rs116624130 · VCV45887

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.15%, afr)

Conditions

Usher syndrome type 1D

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 -14	GERP -3.4
Overall
CADD	3.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.15% African / African-American · 3,113/75,024 alleles

Filtering AF 4.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.98%

Overall 0.321% 5,180/1,613,982 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.15%	24
Ashkenazi Jewishnot grpmax-eligible	1.86%	54
Remaining individualsnot grpmax-eligible	0.547%	183
Middle Eastern	0.495%	202
Admixed American	0.435%	230
European (non-Finnish)	0.0698%	1,432
South Asian	0.0637%	1,570
East Asian	0.00223%	44,884
Finnishnot grpmax-eligible	0.00156%	64,014

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.Gly68=
Coding: c.204C>T
MANE Select: NM_022124
dbSNP: rs116624130
Type: single nucleotide variant
Location: chr10:71510140 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 68: the cadherin 1 domain

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

Disease context

Usher syndrome type 1D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 12

Similar variants

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
CDH23 p.Arg3189Gln 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-gly68 (accessed [today's date]).

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