Is CDH23 p.Ala3068= (c.9204G>A) pathogenic?

CDH23 p.Ala3068= (c.9204G>A) is classified Benign/Likely benign in CDH23 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Rare (popmax 0.974%, afr); Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Ala3068= (c.9204G>A)?

CDH23 p.Ala3068= (c.9204G>A) is associated with Usher syndrome type 1 (ClinVar).

How common is CDH23 p.Ala3068= (c.9204G>A) in the general population?

CDH23 p.Ala3068= (c.9204G>A) is rare (popmax 0.974%, afr) (gnomAD).

How is Usher syndrome inherited?

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

CDH23 p.Ala3068=

c.9204G>A · rs192266658 · VCV162952

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.974%, afr)

Conditions

Usher syndrome type 1

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 -0.41	GERP -3.3, phastCons 0.006
Overall
CADD	7.668	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.974% African / African-American · 731/75,014 alleles

Filtering AF 0.916% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.893%

Overall 0.0508% 820/1,613,926 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.974%	103
Admixed American	0.05%	2,001
Remaining individualsnot grpmax-eligible	0.048%	2,083
Middle Eastern	0.0165%	6,062
Finnishnot grpmax-eligible	0.00312%	32,001
European (non-Finnish)	0.00212%	47,195
South Asian	0.0011%	91,086

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.Ala3068=
Coding: c.9204G>A
MANE Select: NM_022124
dbSNP: rs192266658
Type: single nucleotide variant
Location: chr10:71811516 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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.Ala3068Val 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
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-ala3068 (accessed [today's date]).

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