Is CDH23 p.Arg1811Gln (c.5432G>A) pathogenic?

CDH23 p.Arg1811Gln (c.5432G>A) is classified Uncertain significance in CDH23 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-06-20). AlphaMissense: ambiguous (0.5586); Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with CDH23 p.Arg1811Gln (c.5432G>A)?

CDH23 p.Arg1811Gln (c.5432G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDH23 p.Arg1811Gln (c.5432G>A) in the general population?

CDH23 p.Arg1811Gln (c.5432G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CDH23 p.Arg1811Gln (c.5432G>A)?

AlphaMissense predicts ambiguous (score 0.5586) — an in-silico prediction, not a clinical call.

CDH23 p.Arg1811Gln

c.5432G>A · rs776972162 · VCV1403804

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5586 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5586	ambiguous
REVEL	0.739	pathogenic-leaning
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	33.0	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 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00161% 26/1,613,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
Admixed American	0.0117%	8,571
African / African-American	0.004%	24,973
Remaining individualsnot grpmax-eligible	0.0032%	31,228
South Asian	0.0011%	91,082
European (non-Finnish)	0.000932%	107,256

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.Arg1811Gln
Coding: c.5432G>A
MANE Select: NM_022124
dbSNP: rs776972162
Type: single nucleotide variant
Location: chr10:71784350 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1811: the cadherin 17 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.Arg1811Trp Uncertain significance ★★ same residue
CDH23 p.Arg1811= 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
CDH23 p.Ala1974Thr 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-arg1811gln (accessed [today's date]).

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