Is CDH3 p.Asp807Asn (c.2419G>A) pathogenic?

CDH3 p.Asp807Asn (c.2419G>A) is classified Conflicting classifications of pathogenicity in CDH3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2023-06-27). AlphaMissense: likely benign (0.0698); Ultra-rare (popmax 0.0713%, eas); Associated with EEM syndrome.

What condition is associated with CDH3 p.Asp807Asn (c.2419G>A)?

CDH3 p.Asp807Asn (c.2419G>A) is associated with EEM syndrome (ClinVar).

How common is CDH3 p.Asp807Asn (c.2419G>A) in the general population?

CDH3 p.Asp807Asn (c.2419G>A) is ultra-rare (popmax 0.0713%, eas) (gnomAD).

What do computational predictors say about CDH3 p.Asp807Asn (c.2419G>A)?

AlphaMissense predicts likely benign (score 0.0698) — an in-silico prediction, not a clinical call.

CDH3 p.Asp807Asn

c.2419G>A · rs535174122 · VCV320254

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0698 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0713%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EEM syndrome

Computational evidence

Protein change
AlphaMissense	0.0698	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -9.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.71	GERP -2.3, phastCons 0.077
Overall
CADD	16.64	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 0.0713% East Asian · 32/44,886 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0452%

Overall 0.00273% 44/1,614,212 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0713%	1,403
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Admixed American	0.005%	20,009
South Asian	0.0022%	45,540
European (non-Finnish)	0.000254%	393,342

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.Asp807Asn
Coding: c.2419G>A
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs535174122
Type: single nucleotide variant
Location: chr16:68698329 (GRCh38)
Structure: AlphaFold pLDDT 78.70

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

Disease context

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

Similar variants

CDH3 p.Asp807Gly Uncertain significance ★★ ⚠ same residue
CDH3 p.Asp807Glu Uncertain significance ★ ⚠ same residue
CDH3 p.Glu708Ter Likely pathogenic ★★ same condition
CDH3 c.1571-7C>G Uncertain significance ★★ same condition
CDH3 c.45+6C>T Uncertain significance ★★ same condition
CDH3 c.867+6T>C Uncertain significance ★★ same condition
CDH3 p.Ala159Thr Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala34Thr Uncertain significance ★★ ⚠ same condition

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-asp807asn (accessed [today's date]).

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