Is CDH23 p.Arg1151Trp (c.3451C>T) pathogenic?

CDH23 p.Arg1151Trp (c.3451C>T) is classified Uncertain significance in CDH23 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-04). AlphaMissense: likely benign (0.1243); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with CDH23 p.Arg1151Trp (c.3451C>T)?

CDH23 p.Arg1151Trp (c.3451C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDH23 p.Arg1151Trp (c.3451C>T) in the general population?

CDH23 p.Arg1151Trp (c.3451C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CDH23 p.Arg1151Trp (c.3451C>T)?

AlphaMissense predicts likely benign (score 0.1243) — an in-silico prediction, not a clinical call.

CDH23 p.Arg1151Trp

c.3451C>T · rs757628798 · VCV2142695

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1243 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1243	likely benign
REVEL	0.325	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,910 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00211% 34/1,613,886 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
African / African-Americangrpmax	0.004%	24,970
European (non-Finnish)	0.00229%	43,700
Remaining individualsnot grpmax-eligible	0.0016%	62,466
Finnishnot grpmax-eligible	0.00156%	64,026

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1151Trp
Coding: c.3451C>T
MANE Select: NM_001164375 · reported on NM_022124
dbSNP: rs757628798
Type: single nucleotide variant
Location: chr10:71725392 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-arg1151trp (accessed [today's date]).

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