Is CDH23 p.Val1800Glu (c.5399T>A) pathogenic?

CDH23 p.Val1800Glu (c.5399T>A) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.1356); Ultra-rare (popmax 0.0312%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDH23 p.Val1800Glu (c.5399T>A)?

CDH23 p.Val1800Glu (c.5399T>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDH23 p.Val1800Glu (c.5399T>A) in the general population?

CDH23 p.Val1800Glu (c.5399T>A) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about CDH23 p.Val1800Glu (c.5399T>A)?

AlphaMissense predicts likely benign (score 0.1356) — an in-silico prediction, not a clinical call.

CDH23 p.Val1800Glu

c.5399T>A · rs540755001 · VCV2141584

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1356 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1356	likely benign
REVEL	0.134	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 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	20.4	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 0.0312% East Asian · 14/44,844 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00136% 22/1,613,522 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,203
Remaining individualsnot grpmax-eligible	0.0112%	8,925
Admixed American	0.00167%	59,992

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.Val1800Glu
Coding: c.5399T>A
MANE Select: NM_022124
dbSNP: rs540755001
Type: single nucleotide variant
Location: chr10:71784317 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1800: 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.Val1800Leu Uncertain significance ★ ⚠ same residue
CDH23 p.Val1800Met Uncertain significance ★ ⚠ same residue
CDH23 p.Val1800= 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-val1800glu (accessed [today's date]).

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