Is CDH2 p.Asp883Asn (c.2647G>A) pathogenic?

CDH2 p.Asp883Asn (c.2647G>A) is classified Uncertain significance in CDH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-14). AlphaMissense: ambiguous (0.44); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDH2 p.Asp883Asn (c.2647G>A)?

CDH2 p.Asp883Asn (c.2647G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDH2 p.Asp883Asn (c.2647G>A) in the general population?

CDH2 p.Asp883Asn (c.2647G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CDH2 p.Asp883Asn (c.2647G>A)?

AlphaMissense predicts ambiguous (score 0.44) — an in-silico prediction, not a clinical call.

CDH2 p.Asp883Asn

c.2647G>A · rs377612781 · VCV1794265

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.44 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.44	ambiguous
REVEL	0.575	indeterminate
SaProt	LLR -11.31	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 0.01 · regional, not allelic
Overall
CADD	24.8	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 0.00167% Admixed American · 1/59,942 alleles

Overall 0.000186% 3/1,613,402 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,942
Remaining individualsnot grpmax-eligible	0.0016%	62,454
African / African-American	0.00134%	74,838

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.Asp883Asn
Coding: c.2647G>A
MANE Select: NM_001792
dbSNP: rs377612781
Type: single nucleotide variant
Location: chr18:27952227 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 883: the 'disordered' region

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.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
CDH2 p.Ala418Thr Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala610Thr Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala825Val 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-asp883asn (accessed [today's date]).

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