Is CDH3 p.Asp616= (c.1848C>T) pathogenic?

CDH3 p.Asp616= (c.1848C>T) is classified Conflicting classifications of pathogenicity in CDH3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-03-27). Ultra-rare (popmax 0.0164%, mid); Associated with EEM syndrome.

What condition is associated with CDH3 p.Asp616= (c.1848C>T)?

CDH3 p.Asp616= (c.1848C>T) is associated with EEM syndrome (ClinVar).

How common is CDH3 p.Asp616= (c.1848C>T) in the general population?

CDH3 p.Asp616= (c.1848C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CDH3 p.Asp616=

c.1848C>T · rs768811436 · VCV320248

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

EEM syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -4.4
Overall
CADD	0.876	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00142% 23/1,614,062 alleles · ultra-rare exomes 21/1,461,862 · genomes 2/152,200 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00267%	37,460
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.00153%	65,558

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.Asp616=
Coding: c.1848C>T
MANE Select: NM_001793
dbSNP: rs768811436
Type: single nucleotide variant
Location: chr16:68691772 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.71 · 19 PDB
Residue 616: the cadherin 5 domain

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.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
CDH3 p.Ala400Gly Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala414Thr 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-asp616 (accessed [today's date]).

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