Is CDH23 p.Thr1979= (c.5937G>A) pathogenic?

CDH23 p.Thr1979= (c.5937G>A) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-08). Ultra-rare (popmax 0.03%, amr); Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Thr1979= (c.5937G>A)?

CDH23 p.Thr1979= (c.5937G>A) is associated with autosomal recessive nonsyndromic hearing loss 12, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Thr1979= (c.5937G>A) in the general population?

CDH23 p.Thr1979= (c.5937G>A) is ultra-rare (popmax 0.03%, amr) (gnomAD).

CDH23 p.Thr1979=

c.5937G>A · rs397517347 · VCV45996

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

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 -4.5	GERP -3.1
Overall
CADD	2.455	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/60,000 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00316% 51/1,613,656 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,333
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0128%	7,807
European (non-Finnish)	0.00203%	49,160

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.Thr1979=
Coding: c.5937G>A
MANE Select: NM_022124
dbSNP: rs397517347
Type: single nucleotide variant
Location: chr10:71790301 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1979: the cadherin 19 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 1D

Similar variants

CDH23 p.Thr1979Met Conflicting classifications of pathogenicity ★ ⚠ 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
CDH23 p.Arg301Gln 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-thr1979 (accessed [today's date]).

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