Is CDH23 p.Thr1083= (c.3249G>A) pathogenic?

CDH23 p.Thr1083= (c.3249G>A) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-02). Low-frequency (popmax 2.31%, afr); Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Thr1083= (c.3249G>A)?

CDH23 p.Thr1083= (c.3249G>A) is associated with autosomal recessive nonsyndromic hearing loss 12, Usher syndrome type 1, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Thr1083= (c.3249G>A) in the general population?

CDH23 p.Thr1083= (c.3249G>A) is low-frequency (popmax 2.31%, afr) (gnomAD).

CDH23 p.Thr1083=

c.3249G>A · rs79805606 · VCV45911

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.31%, afr)

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 looked up on this page · why
Constraint at this position
Conservation	phyloP -20	GERP -4.7
Overall
CADD	0.008	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.31% African / African-American · 1,733/75,064 alleles

Filtering AF 2.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.18%

Overall 0.122% 1,965/1,613,646 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.31%	43
Remaining individualsnot grpmax-eligible	0.174%	573
Admixed American	0.138%	723
Middle Eastern	0.0495%	2,020
South Asian	0.0187%	5,357
East Asian	0.00223%	44,870
European (non-Finnish)	0.00161%	62,099

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.Thr1083=
Coding: c.3249G>A
MANE Select: NM_001164375 · reported on NM_022124
dbSNP: rs79805606
Type: single nucleotide variant
Location: chr10:71712693 (GRCh38)

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

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-thr1083 (accessed [today's date]).

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