Is CDH3 p.Arg747Leu (c.2240G>T) pathogenic?

CDH3 p.Arg747Leu (c.2240G>T) is classified Uncertain significance in CDH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). AlphaMissense: ambiguous (0.5111); Very rare (popmax 0.000932%, nfe).

How common is CDH3 p.Arg747Leu (c.2240G>T) in the general population?

CDH3 p.Arg747Leu (c.2240G>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about CDH3 p.Arg747Leu (c.2240G>T)?

AlphaMissense predicts ambiguous (score 0.5111) — an in-silico prediction, not a clinical call.

CDH3 p.Arg747Leu

c.2240G>T · rs772291014 · VCV1487799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5111 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5111	ambiguous
REVEL	0.681	pathogenic-leaning
SaProt	LLR -9.26	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	28.8	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 0.000932% European (non-Finnish) · 11/1,180,038 alleles

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

Overall 0.000752% 11/1,461,874 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: CDH3
Protein: p.Arg747Leu
Coding: c.2240G>T
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs772291014
Type: single nucleotide variant
Location: chr16:68695883 (GRCh38)
Structure: AlphaFold pLDDT 78.70

Full CDH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH3 p.Arg747= Benign ★★ same residue
CDH3 p.Arg747Gln Uncertain significance ★ ⚠ same residue
CDH3 p.Arg747Trp Uncertain significance ★ ⚠ same residue
CDH3 p.Arg747Lys Uncertain significance ★ same residue
CDH3 c.1796-2A>G Pathogenic ★★ same type
CDH3 c.691+1G>A Pathogenic/Likely pathogenic ★★ same type
CDH3 p.Arg103Ter Pathogenic ★★ same type
CDH3 p.Arg221Ter Pathogenic ★★ 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/cdh3-p-arg747leu (accessed [today's date]).

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