Is CDH23 p.Ser1833= (c.5499C>T) pathogenic?

CDH23 p.Ser1833= (c.5499C>T) is classified Likely benign in CDH23 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-02-19). Very rare (popmax 0.000339%, nfe).

How common is CDH23 p.Ser1833= (c.5499C>T) in the general population?

CDH23 p.Ser1833= (c.5499C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

CDH23 p.Ser1833=

c.5499C>T · rs397517339 · VCV45981

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 1.8	GERP 1.9, phastCons 1
Overall
CADD	12.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,100 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,612,514 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.Ser1833=
Coding: c.5499C>T
MANE Select: NM_022124
dbSNP: rs397517339
Type: single nucleotide variant
Location: chr10:71784417 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1833: the cadherin 17 domain

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

Similar variants

CDH23 p.Ser1833Cys Uncertain significance ★ same residue
CDH23 p.Arg2029Trp Pathogenic ★★★ ⚠ same type
CDH23 p.Asp127Gly Likely pathogenic ★★★ same type
CDH23 p.Glu956Lys Pathogenic ★★★ same type
CDH23 p.Pro240Leu Pathogenic ★★★ same type
CDH23 c.1515-12G>A Uncertain significance ★★★ same type
CDH23 p.Ala3190Val Uncertain significance ★★★ same type
CDH23 p.Arg301Gln Uncertain significance ★★★ same type

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-ser1833 (accessed [today's date]).

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