Is CDH23 p.Glu2307Lys (c.6919G>A) pathogenic?

CDH23 p.Glu2307Lys (c.6919G>A) is classified Likely pathogenic in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely pathogenic (0.9754); Very rare (popmax 8.48e-05%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Glu2307Lys (c.6919G>A)?

CDH23 p.Glu2307Lys (c.6919G>A) is associated with autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

How common is CDH23 p.Glu2307Lys (c.6919G>A) in the general population?

CDH23 p.Glu2307Lys (c.6919G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CDH23 p.Glu2307Lys (c.6919G>A)?

AlphaMissense predicts likely pathogenic (score 0.9754) — an in-silico prediction, not a clinical call.

CDH23 p.Glu2307Lys

c.6919G>A · VCV3601564

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9754 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

autosomal recessive nonsyndromic hearing loss 12

Computational evidence

Protein change
AlphaMissense	0.9754	likely pathogenic ✓ concordant with ClinVar · top 7% in CDH23
REVEL	0.87	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	31.0	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 8.48e-05% European (non-Finnish) · 1/1,179,866 alleles

Overall 0.000657% 1/152,208 alleles · very rare

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.Glu2307Lys
Coding: c.6919G>A
MANE Select: NM_022124
Type: single nucleotide variant
Location: chr10:71798443 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2307: the cadherin 22 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

Similar variants

CDH23 p.Glu2307Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH23 p.Glu2307= Likely benign ★ 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 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-glu2307lys (accessed [today's date]).

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