Is CDH23 p.Pro2707= (c.8121G>T) pathogenic?

CDH23 p.Pro2707= (c.8121G>T) is classified Benign/Likely benign in CDH23 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-01). Rare (popmax 0.923%, sas); Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Pro2707= (c.8121G>T)?

CDH23 p.Pro2707= (c.8121G>T) is associated with autosomal recessive nonsyndromic hearing loss 12, Usher syndrome type 1, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Pro2707= (c.8121G>T) in the general population?

CDH23 p.Pro2707= (c.8121G>T) is rare (popmax 0.923%, sas) (gnomAD).

CDH23 p.Pro2707=

c.8121G>T · rs377535432 · VCV735477

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.923%, sas)

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 -5.2	GERP -3.4
Overall
CADD	0.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.923% South Asian · 795/86,098 alleles

Filtering AF 0.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.849%

Overall 0.0613% 967/1,578,332 alleles · rare exomes 916/1,426,086 · genomes 51/152,246 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.923%	108
Middle Eastern	0.416%	241
Remaining individualsnot grpmax-eligible	0.0932%	1,073
Admixed American	0.0237%	4,223
European (non-Finnish)	0.00645%	15,497
East Asian	0.00466%	21,469

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.Pro2707=
Coding: c.8121G>T
MANE Select: NM_022124
dbSNP: rs377535432
Type: single nucleotide variant
Location: chr10:71806224 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2707: the cadherin 25 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 pituitary adenoma 5, multiple types

Similar variants

CDH23 p.Pro2707Ser Uncertain significance ★ same residue
CDH23 p.Pro2707Leu Benign/Likely benign ★★ 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-pro2707 (accessed [today's date]).

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