Is CDH23 p.Arg1060Pro (c.3179G>C) pathogenic?

CDH23 p.Arg1060Pro (c.3179G>C) is classified Uncertain significance in CDH23 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-03). AlphaMissense: likely pathogenic (0.9973); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with CDH23 p.Arg1060Pro (c.3179G>C)?

CDH23 p.Arg1060Pro (c.3179G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CDH23 p.Arg1060Pro (c.3179G>C) in the general population?

CDH23 p.Arg1060Pro (c.3179G>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CDH23 p.Arg1060Pro (c.3179G>C)?

AlphaMissense predicts likely pathogenic (score 0.9973) — an in-silico prediction, not a clinical call.

CDH23 p.Arg1060Pro

c.3179G>C · rs536438868 · VCV1060503

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9973 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9973	likely pathogenic · top 1% in CDH23
REVEL	0.796	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 1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,946 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,613,850 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.Arg1060Pro
Coding: c.3179G>C
MANE Select: NM_022124
dbSNP: rs536438868
Type: single nucleotide variant
Location: chr10:71709170 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1060: a UniProt-annotated variant site (in dfnb12); the cadherin 10 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH23 p.Arg1060Gln Uncertain significance ★★ ⚠ same residue
CDH23 p.Arg1060Trp Conflicting classifications of pathogenicity ★ same residue
CDH23 p.Arg1060= Likely benign ★ same residue
CDH23 p.Ala129Thr Uncertain significance ★★ ⚠ same condition
CDH23 p.Ala1464Glu Uncertain significance ★★ ⚠ same condition
CDH23 p.Ala1482Val Uncertain significance ★★ ⚠ same condition
CDH23 p.Ala1673Val Uncertain significance ★★ same condition
CDH23 p.Ala1878Thr 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-arg1060pro (accessed [today's date]).

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