Is CDH2 p.Asp436Glu (c.1308C>G) pathogenic?

CDH2 p.Asp436Glu (c.1308C>G) is classified Uncertain significance in CDH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-28). AlphaMissense: ambiguous (0.4358); Absent from gnomAD v4.1.

How common is CDH2 p.Asp436Glu (c.1308C>G) in the general population?

CDH2 p.Asp436Glu (c.1308C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH2 p.Asp436Glu (c.1308C>G)?

AlphaMissense predicts ambiguous (score 0.4358) — an in-silico prediction, not a clinical call.

CDH2 p.Asp436Glu

c.1308C>G · rs2510799020 · VCV2878752

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4358 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4358	ambiguous
REVEL	0.356	indeterminate
SaProt	LLR -11.24	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.13, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 27 kb · p 4e-09 · regional, not allelic
Overall
CADD	24.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDH2
Protein: p.Asp436Glu
Coding: c.1308C>G
MANE Select: NM_001792
dbSNP: rs2510799020
Type: single nucleotide variant
Location: chr18:27992691 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 436: the cadherin 3 domain

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

Similar variants

CDH2 p.Asp436Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH2 p.Asp436Tyr Uncertain significance ★ ⚠ same residue
CDH2 c.1344+1G>A Pathogenic/Likely pathogenic ★★ same type
CDH2 c.702+1G>A Pathogenic/Likely pathogenic ★★ same type
CDH2 p.Tyr676Cys Pathogenic ★★ same type
CDH2 c.61-1G>A Uncertain significance ★★ same type
CDH2 c.848-16T>G Uncertain significance ★★ same type
CDH2 p.Ala106Val Uncertain significance ★★ ⚠ 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/cdh2-p-asp436glu (accessed [today's date]).

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