Is CDH10 p.Pro729Arg (c.2186C>G) pathogenic?

CDH10 p.Pro729Arg (c.2186C>G) is classified Uncertain significance in CDH10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: likely pathogenic (0.8857); Very rare (popmax 0.00334%, amr).

How common is CDH10 p.Pro729Arg (c.2186C>G) in the general population?

CDH10 p.Pro729Arg (c.2186C>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about CDH10 p.Pro729Arg (c.2186C>G)?

AlphaMissense predicts likely pathogenic (score 0.8857) — an in-silico prediction, not a clinical call.

CDH10 p.Pro729Arg

c.2186C>G · VCV3830011

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8857 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8857	likely pathogenic
REVEL	0.866	moderately pathogenic-leaning
SaProt	LLR -14.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 4,005 bp · p 0.97 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00334% Admixed American · 2/59,960 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00124% 20/1,613,776 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,980
Remaining individualsnot grpmax-eligible	0.0032%	31,239
Finnishnot grpmax-eligible	0.00312%	32,015
European (non-Finnish)	0.00119%	84,280

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: CDH10
Protein: p.Pro729Arg
Coding: c.2186C>G
MANE Select: NM_006727
Type: single nucleotide variant
Location: chr5:24487844 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 78.29

Full CDH10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH10 p.Met316Ile Uncertain significance ★★ ⚠ same type
CDH10 p.Thr159Met Uncertain significance ★★ ⚠ same type
CDH10 p.Glu469= Benign ★★ same type
CDH10 p.Gly673= Benign ★★ same type
CDH10 p.Ala296Thr Uncertain significance ★ ⚠ same type
CDH10 p.Ala501Val Uncertain significance ★ ⚠ same type
CDH10 p.Ala530Val Uncertain significance ★ ⚠ same type
CDH10 p.Arg128Cys 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/cdh10-p-pro729arg (accessed [today's date]).

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