Is CDH23 p.Thr1401= (c.4203C>T) pathogenic?

CDH23 p.Thr1401= (c.4203C>T) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.53%, eas); Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Thr1401= (c.4203C>T)?

CDH23 p.Thr1401= (c.4203C>T) is associated with autosomal recessive nonsyndromic hearing loss 12, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Thr1401= (c.4203C>T) in the general population?

CDH23 p.Thr1401= (c.4203C>T) is low-frequency (popmax 1.53%, eas) (gnomAD).

CDH23 p.Thr1401=

c.4203C>T · rs202166096 · VCV178602

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.53%, eas)

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 looked up on this page · why
Pangolin	Δ0.23	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP -12	GERP -4.6
Overall
CADD	1.162	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.53% East Asian · 683/44,516 alleles

Filtering AF 1.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4%

Overall 0.0864% 1,388/1,606,092 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.53%	65
South Asian	0.247%	406
Remaining individualsnot grpmax-eligible	0.0933%	1,072
European (non-Finnish)	0.0353%	2,834
Middle Eastern	0.0165%	6,048
Admixed American	0.00848%	11,798
African / African-American	0.004%	24,983
Finnishnot grpmax-eligible	0.00316%	31,598

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.Thr1401=
Coding: c.4203C>T
MANE Select: NM_001164375 · reported on NM_022124
dbSNP: rs202166096
Type: single nucleotide variant
Location: chr10:71734338 (GRCh38)

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 1D

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-thr1401 (accessed [today's date]).

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