Is CDH23 p.Ser351= (c.1053C>T) pathogenic?

CDH23 p.Ser351= (c.1053C>T) is classified Benign in CDH23 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 24%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 1D.

What condition is associated with CDH23 p.Ser351= (c.1053C>T)?

CDH23 p.Ser351= (c.1053C>T) is associated with Usher syndrome type 1D, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

CDH23 p.Ser351=

Q: How common is CDH23 p.Ser351= (c.1053C>T) in the general population?

CDH23 p.Ser351= (c.1053C>T) is common (popmax 24%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1053C>T · rs7903475 · VCV44113

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 24%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Usher syndrome type 1D

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 -13	GERP -3.5
Overall
CADD	0.852	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24% African / African-American · 17,943/74,914 alleles

Filtering AF 23.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.5%

Overall 1.34% 21,673/1,613,836 alleles · common exomes 11,155/1,461,692 · genomes 10,518/152,144 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	24%	4
Middle Eastern	1.93%	52
Remaining individualsnot grpmax-eligible	1.88%	53
Admixed American	1.76%	57
Ashkenazi Jewishnot grpmax-eligible	1.4%	71
European (non-Finnish)	0.0765%	1,307
South Asian	0.0681%	1,469
East Asian	0.00446%	22,440

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.Ser351=
Coding: c.1053C>T
MANE Select: NM_022124
dbSNP: rs7903475
Type: single nucleotide variant
Location: chr10:71617312 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 351: the cadherin 4 domain

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

Disease context

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

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 12

Similar variants

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
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-ser351 (accessed [today's date]).

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