Is CDH23 p.Ala605Val (c.1814C>T) pathogenic?

CDH23 p.Ala605Val (c.1814C>T) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0849); Rare (popmax 0.742%, mid); Associated with Usher syndrome.

What condition is associated with CDH23 p.Ala605Val (c.1814C>T)?

CDH23 p.Ala605Val (c.1814C>T) is associated with Usher syndrome, Usher syndrome type 1, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Ala605Val (c.1814C>T) in the general population?

CDH23 p.Ala605Val (c.1814C>T) is rare (popmax 0.742%, mid) (gnomAD).

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.Ala605Val (c.1814C>T)?

AlphaMissense predicts likely benign (score 0.0849) — an in-silico prediction, not a clinical call.

CDH23 p.Ala605Val

c.1814C>T · rs201475055 · VCV45883

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0849 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.742%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Usher syndrome

Computational evidence

Protein change
AlphaMissense	0.0849	likely benign
REVEL	0.073	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 1.4	GERP 0.53, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	18.24	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 0.742% Middle Eastern · 45/6,062 alleles

Filtering AF 0.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.509%

Overall 0.0573% 925/1,613,550 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.742%	135
South Asian	0.426%	235
Ashkenazi Jewishnot grpmax-eligible	0.378%	264
Admixed American	0.122%	821
Remaining individualsnot grpmax-eligible	0.0864%	1,157
European (non-Finnish)	0.0211%	4,738
African / African-American	0.004%	25,026
Finnishnot grpmax-eligible	0.00313%	31,990

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.Ala605Val
Coding: c.1814C>T
MANE Select: NM_022124
dbSNP: rs201475055
Type: single nucleotide variant
Location: chr10:71679448 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 605: the cadherin 6 domain; a β-strand

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

Disease context

Usher 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-ala605val (accessed [today's date]).

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