Is CDH23 p.Asp990= (c.2970C>T) pathogenic?

CDH23 p.Asp990= (c.2970C>T) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-06-01). Rare (popmax 0.548%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Asp990= (c.2970C>T)?

CDH23 p.Asp990= (c.2970C>T) is associated with autosomal recessive nonsyndromic hearing loss 12, Usher syndrome type 1, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Asp990= (c.2970C>T) in the general population?

CDH23 p.Asp990= (c.2970C>T) is rare (popmax 0.548%, nfe) (gnomAD).

CDH23 p.Asp990=

c.2970C>T · rs56216952 · VCV44110

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.548%, nfe)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.2	GERP -4.8
Overall
CADD	6.389	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.548% European (non-Finnish) · 6,442/1,175,066 alleles

Filtering AF 0.537% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.532%

Overall 0.442% 7,085/1,602,638 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	4.28%	23
European (non-Finnish)grpmax	0.548%	182
Finnishnot grpmax-eligible	0.449%	223
Remaining individualsnot grpmax-eligible	0.333%	300
Middle Eastern	0.0828%	1,208
Admixed American	0.07%	1,428
African / African-American	0.0521%	1,918
South Asian	0.0282%	3,550
Ashkenazi Jewishnot grpmax-eligible	0.0171%	5,857

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp990=
Coding: c.2970C>T
MANE Select: NM_022124
dbSNP: rs56216952
Type: single nucleotide variant
Location: chr10:71706913 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 990: a UniProt-annotated variant site (in dfnb12); the cadherin 9 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 1 Usher syndrome type 1D

Similar variants

CDH23 p.Asp990Asn 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-asp990 (accessed [today's date]).

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