Is CDH23 p.Phe2664del (c.7987TTC[1]) pathogenic?

CDH23 p.Phe2664del (c.7987TTC[1]) is classified Pathogenic/Likely pathogenic in CDH23 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-04-26). Very rare (popmax 0.00401%, afr); Associated with autosomal recessive nonsyndromic hearing loss 12.

How common is CDH23 p.Phe2664del (c.7987TTC[1]) in the general population?

CDH23 p.Phe2664del (c.7987TTC[1]) is very rare (popmax 0.00401%, afr) (gnomAD).

CDH23 p.Phe2664del

Q: What condition is associated with CDH23 p.Phe2664del (c.7987TTC[1])?

CDH23 p.Phe2664del (c.7987TTC[1]) is associated with autosomal recessive nonsyndromic hearing loss 12, Usher syndrome type 1, Usher syndrome type 1D (ClinVar).

c.7987TTC[1] · rs774559018 · VCV996634

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00401%, 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 · substitutions only
Constraint at this position
Conservation	phyloP -0.43	GERP 0.75, phastCons 0.003
Overall
CADD	17.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,862 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00062% 10/1,612,212 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,954
South Asian	0.0022%	45,484
Remaining individualsnot grpmax-eligible	0.0016%	62,376
Finnishnot grpmax-eligible	0.00157%	63,752
European (non-Finnish)	0.000254%	393,009

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.Phe2664del
Coding: c.7987TTC[1]
MANE Select: NM_022124
dbSNP: rs774559018
Type: Microsatellite
Location: chr10:71805920 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2664: 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 hearing loss, autosomal recessive pituitary adenoma 5, multiple types

Similar variants

CDH23 p.Gln462fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Gly2156fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Phe3083fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ser3157fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Val2274fs Likely pathogenic ★★ same condition
CDH23 p.Lys2775del Uncertain significance ★★ same condition
CDH23 p.Phe2664Ile Uncertain significance ★★ ⚠ same residue
CDH23 c.9278_9278+3del Pathogenic ★ 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-phe2664del (accessed [today's date]).

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