Is CDH23 p.Glu2044Lys (c.6130G>A) pathogenic?

CDH23 p.Glu2044Lys (c.6130G>A) is classified Benign/Likely benign in CDH23 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0699); Common (popmax 57%, eas) — too common for a highly-penetrant pathogenic allele; Associated with retinitis pigmentosa-deafness syndrome.

What condition is associated with CDH23 p.Glu2044Lys (c.6130G>A)?

CDH23 p.Glu2044Lys (c.6130G>A) is associated with retinitis pigmentosa-deafness syndrome, Usher syndrome type 1, Usher syndrome type 1D (ClinVar).

How is Usher syndrome inherited?

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

What do computational predictors say about CDH23 p.Glu2044Lys (c.6130G>A)?

AlphaMissense predicts likely benign (score 0.0699) — an in-silico prediction, not a clinical call.

CDH23 p.Glu2044Lys

Q: How common is CDH23 p.Glu2044Lys (c.6130G>A) in the general population?

CDH23 p.Glu2044Lys (c.6130G>A) is common (popmax 57%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6130G>A · rs10466026 · VCV46002

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.0699 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 57%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

retinitis pigmentosa-deafness syndrome

Computational evidence

Protein change
AlphaMissense	0.0699	likely benign
REVEL	0.177	moderately 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 8.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	24.9	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 57% East Asian · 25,567/44,824 alleles

Filtering AF 56.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 56.2%

Overall 28.9% 465,323/1,612,844 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	57%	2
Admixed American	39.6%	3
Amishnot grpmax-eligible	38.3%	3
Finnishnot grpmax-eligible	34.7%	3
Remaining individualsnot grpmax-eligible	28.7%	3
European (non-Finnish)	27.8%	4
African / African-American	26.6%	4
South Asian	22.8%	4
Ashkenazi Jewishnot grpmax-eligible	21.2%	5
Middle Eastern	16%	6

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.Glu2044Lys
Coding: c.6130G>A
MANE Select: NM_022124
dbSNP: rs10466026
Type: single nucleotide variant
Location: chr10:71791212 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2044: a UniProt-annotated variant site (in); the cadherin 19 domain

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

Disease context

retinitis pigmentosa-deafness syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

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-glu2044lys (accessed [today's date]).

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