Is CDH23 p.Ala2870Val (c.8609C>T) pathogenic?

CDH23 p.Ala2870Val (c.8609C>T) is classified Uncertain significance in CDH23 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-25). AlphaMissense: likely pathogenic (0.6411); Very rare (popmax 8.51e-05%, nfe).

How common is CDH23 p.Ala2870Val (c.8609C>T) in the general population?

CDH23 p.Ala2870Val (c.8609C>T) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about CDH23 p.Ala2870Val (c.8609C>T)?

AlphaMissense predicts likely pathogenic (score 0.6411) — an in-silico prediction, not a clinical call.

CDH23 p.Ala2870Val

c.8609C>T · rs1168332101 · VCV1431120

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6411 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.6411	likely pathogenic
REVEL	0.622	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 12 kb · p 0.86 · regional, not allelic
Overall
CADD	28.1	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 8.51e-05% European (non-Finnish) · 1/1,175,218 alleles

Overall 6.89e-05% 1/1,451,426 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.Ala2870Val
Coding: c.8609C>T
MANE Select: NM_022124
dbSNP: rs1168332101
Type: single nucleotide variant
Location: chr10:71807894 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2870: the cadherin 27 domain

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

Similar variants

CDH23 p.Ala2870Thr Uncertain significance ★ same residue
CDH23 p.Ala2870= Likely benign ★ same residue
CDH23 p.Arg2029Trp Pathogenic ★★★ ⚠ same type
CDH23 p.Asp127Gly Likely pathogenic ★★★ same type
CDH23 p.Glu956Lys Pathogenic ★★★ same type
CDH23 p.Pro240Leu Pathogenic ★★★ same type
CDH23 c.1515-12G>A Uncertain significance ★★★ same type
CDH23 p.Ala3190Val Uncertain significance ★★★ ⚠ same type

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-ala2870val (accessed [today's date]).

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