Is CDH2 p.Asn190Ser (c.569A>G) pathogenic?

CDH2 p.Asn190Ser (c.569A>G) is classified Uncertain significance in CDH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-04). AlphaMissense: likely benign (0.0723); Absent from gnomAD v4.1.

How common is CDH2 p.Asn190Ser (c.569A>G) in the general population?

CDH2 p.Asn190Ser (c.569A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH2 p.Asn190Ser (c.569A>G)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

CDH2 p.Asn190Ser

c.569A>G · rs1599030865 · VCV1395635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 2,131 bp · p 2.1e-07 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Asn190Ser
Coding: c.569A>G
MANE Select: NM_001792
dbSNP: rs1599030865
Type: single nucleotide variant
Location: chr18:28009850 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 190: the cadherin 1 domain

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

Similar variants

CDH2 p.Asn190= Likely benign ★ 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
CDH2 p.Ala21Val 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-asn190ser (accessed [today's date]).

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