Is CDH23 p.Val66= (c.198G>A) pathogenic?

CDH23 p.Val66= (c.198G>A) is classified Benign/Likely benign in CDH23 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.63%, sas); Associated with Usher syndrome type 1D.

What condition is associated with CDH23 p.Val66= (c.198G>A)?

CDH23 p.Val66= (c.198G>A) is associated with Usher syndrome type 1D, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

How common is CDH23 p.Val66= (c.198G>A) in the general population?

CDH23 p.Val66= (c.198G>A) is low-frequency (popmax 2.63%, sas) (gnomAD).

CDH23 p.Val66=

c.198G>A · rs111033288 · VCV45885

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.63%, sas)

Conditions

Usher syndrome type 1D

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 3.2	GERP 0.59, phastCons 1
Overall
CADD	8.696	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.63% South Asian · 2,398/91,084 alleles

Filtering AF 2.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.51%

Overall 0.278% 4,487/1,614,058 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.63%	38
Middle Eastern	1.35%	74
Remaining individualsnot grpmax-eligible	0.32%	312
Ashkenazi Jewishnot grpmax-eligible	0.25%	400
Admixed American	0.138%	723
European (non-Finnish)	0.136%	735
African / African-American	0.0306%	3,264
Finnishnot grpmax-eligible	0.0297%	3,369
East Asian	0.00668%	14,961

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.Val66=
Coding: c.198G>A
MANE Select: NM_022124
dbSNP: rs111033288
Type: single nucleotide variant
Location: chr10:71510134 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 66: the cadherin 1 domain

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

Disease context

Usher syndrome type 1D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

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-val66 (accessed [today's date]).

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