Is CDH23 p.Arg1502Ter (c.4504C>T) pathogenic?

CDH23 p.Arg1502Ter (c.4504C>T) is classified Likely pathogenic in CDH23 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-04-01). Ultra-rare (popmax 0.0164%, mid); Associated with inherited retinal dystrophy.

What condition is associated with CDH23 p.Arg1502Ter (c.4504C>T)?

CDH23 p.Arg1502Ter (c.4504C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is CDH23 p.Arg1502Ter (c.4504C>T) in the general population?

CDH23 p.Arg1502Ter (c.4504C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CDH23 p.Arg1502Ter

c.4504C>T · rs769742202 · VCV636160

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 37 of 70
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.058	GERP -1, phastCons 0.71
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00161% 26/1,613,614 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0172%	5,797
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0048%	20,820
East Asian	0.00223%	44,888
European (non-Finnish)	0.000848%	117,988

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.Arg1502Ter
Coding: c.4504C>T
MANE Select: NM_022124
dbSNP: rs769742202
Type: single nucleotide variant
Location: chr10:71740837 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1502: the cadherin 14 domain

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH23 c.2398-1G>T Pathogenic/Likely pathogenic ★★ same condition
CDH23 c.6050-9G>A Pathogenic ★★ same condition
CDH23 p.Ala1072Asp Likely pathogenic ★★ same condition
CDH23 p.Asp2148Asn Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Thr2454= Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Tyr2636Ter Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Arg2358Trp Uncertain significance ★★ ⚠ same condition
CDH23 p.Arg2809His 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-arg1502ter (accessed [today's date]).

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