Is CDH23 p.Asp3253Ala (c.9758A>C) pathogenic?

CDH23 p.Asp3253Ala (c.9758A>C) is classified Benign/Likely benign in CDH23 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0982); Low-frequency (popmax 1.37%, afr); Associated with Usher syndrome type 1D.

What condition is associated with CDH23 p.Asp3253Ala (c.9758A>C)?

CDH23 p.Asp3253Ala (c.9758A>C) is associated with Usher syndrome type 1D, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

How common is CDH23 p.Asp3253Ala (c.9758A>C) in the general population?

CDH23 p.Asp3253Ala (c.9758A>C) is low-frequency (popmax 1.37%, afr) (gnomAD).

What do computational predictors say about CDH23 p.Asp3253Ala (c.9758A>C)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

CDH23 p.Asp3253Ala

c.9758A>C · rs140463385 · VCV46079

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.37%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Usher syndrome type 1D

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.269	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 12 kb · p 0.86 · regional, not allelic
Overall
CADD	23.8	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 1.37% African / African-American · 1,028/75,044 alleles

Filtering AF 1.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.27%

Overall 0.175% 2,823/1,611,996 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.37%	73
South Asian	1.02%	98
Middle Eastern	0.76%	132
Ashkenazi Jewishnot grpmax-eligible	0.45%	222
Remaining individualsnot grpmax-eligible	0.288%	347
Admixed American	0.198%	504
European (non-Finnish)	0.0324%	3,087
East Asian	0.00892%	11,212

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.Asp3253Ala
Coding: c.9758A>C
MANE Select: NM_022124
dbSNP: rs140463385
Type: single nucleotide variant
Location: chr10:71814971 (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 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.Asp3253= Conflicting classifications of pathogenicity ★ 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-asp3253ala (accessed [today's date]).

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