Is CDH23 p.Asn1156Ser (c.3467A>G) pathogenic?

CDH23 p.Asn1156Ser (c.3467A>G) is classified Uncertain significance in CDH23 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-10). AlphaMissense: likely benign (0.0506); Very rare (popmax 0.000932%, nfe); Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Asn1156Ser (c.3467A>G)?

CDH23 p.Asn1156Ser (c.3467A>G) is associated with Usher syndrome type 1 (ClinVar).

How common is CDH23 p.Asn1156Ser (c.3467A>G) in the general population?

CDH23 p.Asn1156Ser (c.3467A>G) is very rare (popmax 0.000932%, nfe) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CDH23 p.Asn1156Ser (c.3467A>G)?

AlphaMissense predicts likely benign (score 0.0506) — an in-silico prediction, not a clinical call.

CDH23 p.Asn1156Ser

c.3467A>G · rs375367387 · VCV989825

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0506 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.0506	likely benign
REVEL	0.052	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.44	GERP -4.8
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	1.303	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,900 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,920 alleles · very rare

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.Asn1156Ser
Coding: c.3467A>G
MANE Select: NM_001164375 · reported on NM_022124
dbSNP: rs375367387
Type: single nucleotide variant
Location: chr10:71725408 (GRCh38)

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

Disease context

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

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

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-asn1156ser (accessed [today's date]).

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