Is CDH3 p.Tyr823= (c.2469C>T) pathogenic?

CDH3 p.Tyr823= (c.2469C>T) is classified Conflicting classifications of pathogenicity in CDH3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-18). Rare (popmax 0.129%, eas); Associated with EEM syndrome.

What condition is associated with CDH3 p.Tyr823= (c.2469C>T)?

CDH3 p.Tyr823= (c.2469C>T) is associated with EEM syndrome (ClinVar).

How common is CDH3 p.Tyr823= (c.2469C>T) in the general population?

CDH3 p.Tyr823= (c.2469C>T) is rare (popmax 0.129%, eas) (gnomAD).

CDH3 p.Tyr823=

c.2469C>T · rs576190086 · VCV739418

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.129%, eas)

Conditions

EEM syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.9	GERP -4.4
Overall
CADD	2.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.129% East Asian · 58/44,888 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.093%

Overall 0.00465% 75/1,614,102 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.129%	774
South Asian	0.0022%	45,542
Remaining individualsnot grpmax-eligible	0.0016%	62,492
African / African-American	0.00133%	75,044
European (non-Finnish)	0.0011%	90,767

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.Tyr823=
Coding: c.2469C>T
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs576190086
Type: single nucleotide variant
Location: chr16:68698379 (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.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-tyr823 (accessed [today's date]).

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