Is CDH23 p.Arg3Cys (c.7C>T) pathogenic?

CDH23 p.Arg3Cys (c.7C>T) is classified Benign/Likely benign in CDH23 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0871); Common (popmax 34.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 1D.

What condition is associated with CDH23 p.Arg3Cys (c.7C>T)?

CDH23 p.Arg3Cys (c.7C>T) is associated with Usher syndrome type 1D, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

What do computational predictors say about CDH23 p.Arg3Cys (c.7C>T)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

CDH23 p.Arg3Cys

Q: How common is CDH23 p.Arg3Cys (c.7C>T) in the general population?

CDH23 p.Arg3Cys (c.7C>T) is common (popmax 34.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7C>T · rs7902757 · VCV46042

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 34.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Usher syndrome type 1D

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.077	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 -0.56	GERP -4.3, phastCons 0.001
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	16.02	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 34.9% African / African-American · 25,629/73,416 alleles

Filtering AF 34.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 34.4%

Overall 4.03% 63,043/1,563,838 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	34.9%	3
Middle Eastern	8.59%	12
South Asian	4.93%	20
Remaining individualsnot grpmax-eligible	4.91%	20
Admixed American	4.03%	25
Ashkenazi Jewishnot grpmax-eligible	3.52%	28
Finnishnot grpmax-eligible	2.24%	45
European (non-Finnish)	2.19%	46
Amishnot grpmax-eligible	2.08%	48
East Asian	0.0448%	2,231

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.Arg3Cys
Coding: c.7C>T
MANE Select: NM_022124
dbSNP: rs7902757
Type: single nucleotide variant
Location: chr10:71439838 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3: a UniProt-annotated variant site (in)

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.Arg3His Uncertain significance ★★ ⚠ same residue
CDH23 p.Arg3Leu Uncertain significance ★ ⚠ same residue
CDH23 p.Arg3= 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 c.1515-12G>A 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-arg3cys (accessed [today's date]).

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