Is CDH23 p.Ser2807= (c.8421C>T) pathogenic?

CDH23 p.Ser2807= (c.8421C>T) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.015%, amr); Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Ser2807= (c.8421C>T)?

CDH23 p.Ser2807= (c.8421C>T) is associated with Usher syndrome type 1 (ClinVar).

How common is CDH23 p.Ser2807= (c.8421C>T) in the general population?

CDH23 p.Ser2807= (c.8421C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CDH23 p.Ser2807=

c.8421C>T · rs755841293 · VCV745198

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Conditions

Usher syndrome type 1

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	10.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/60,000 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00105% 17/1,613,892 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,667
Remaining individualsnot grpmax-eligible	0.00801%	12,492
European (non-Finnish)	0.000254%	393,297

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.Ser2807=
Coding: c.8421C>T
MANE Select: NM_022124
dbSNP: rs755841293
Type: single nucleotide variant
Location: chr10:71807628 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2807: the cadherin 26 domain

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

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

CDH23 p.Ser2807Asn Uncertain significance ★ 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
CDH23 p.Arg301Gln Uncertain significance ★★★ same condition
CDH23 p.Arg3189Gln 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-ser2807 (accessed [today's date]).

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