Is CDH23 p.Asp1848= (c.5544C>T) pathogenic?

CDH23 p.Asp1848= (c.5544C>T) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-06-01). Rare (popmax 0.601%, afr); Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Asp1848= (c.5544C>T)?

CDH23 p.Asp1848= (c.5544C>T) is associated with autosomal recessive nonsyndromic hearing loss 12, Usher syndrome type 1, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Asp1848= (c.5544C>T) in the general population?

CDH23 p.Asp1848= (c.5544C>T) is rare (popmax 0.601%, afr) (gnomAD).

CDH23 p.Asp1848=

c.5544C>T · rs142131750 · VCV45986

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.601%, afr)

Conditions

autosomal recessive nonsyndromic hearing loss 12

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 3.3	GERP 1.7, phastCons 1
Overall
CADD	9.905	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.601% African / African-American · 451/75,074 alleles

Filtering AF 0.555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.537%

Overall 0.32% 5,168/1,614,084 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.682%	147
African / African-Americangrpmax	0.601%	166
Middle Eastern	0.445%	225
Ashkenazi Jewishnot grpmax-eligible	0.372%	269
Remaining individualsnot grpmax-eligible	0.339%	295
European (non-Finnish)	0.313%	320
Admixed American	0.197%	509
South Asian	0.133%	753
East Asian	0.00891%	11,221

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp1848=
Coding: c.5544C>T
MANE Select: NM_022124
dbSNP: rs142131750
Type: single nucleotide variant
Location: chr10:71784932 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1848: the cadherin 17 domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 Usher syndrome type 1D

Similar variants

CDH23 p.Asp1848Asn Uncertain significance ★★ ⚠ same residue
CDH23 p.Asp1848His 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.Ala3190Val 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-asp1848 (accessed [today's date]).

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