Is CDH2 p.Asp441= (c.1323C>T) pathogenic?

CDH2 p.Asp441= (c.1323C>T) is classified Likely benign in CDH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-19). Ultra-rare (popmax 0.0217%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDH2 p.Asp441= (c.1323C>T)?

CDH2 p.Asp441= (c.1323C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDH2 p.Asp441= (c.1323C>T) in the general population?

CDH2 p.Asp441= (c.1323C>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

CDH2 p.Asp441=

c.1323C>T · rs748210936 · VCV1542302

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Conditions

Inborn genetic diseases

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 · G>C here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.7	GERP -5.6
Overall
CADD	10.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% Admixed American · 13/59,956 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00217% 35/1,613,138 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,612
African / African-American	0.00668%	14,980
Remaining individualsnot grpmax-eligible	0.0032%	31,227
European (non-Finnish)	0.00119%	84,253
South Asian	0.0011%	90,906

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: CDH2
Protein: p.Asp441=
Coding: c.1323C>T
MANE Select: NM_001792
dbSNP: rs748210936
Type: single nucleotide variant
Location: chr18:27992676 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 441: the cadherin 3 domain

Full CDH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH2 p.Asp441Asn Uncertain significance ★★ ⚠ same residue
CDH2 p.Asp441Tyr Likely pathogenic ★ ⚠ same residue
CDH2 p.Asp441Glu Uncertain significance ★ ⚠ same residue
CDH2 p.Ala21Val Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala294Gly Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala299Thr Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala415Ser Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala418Ser 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/cdh2-p-asp441 (accessed [today's date]).

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