Is CDH2 p.Asn417= (c.1251C>T) pathogenic?

CDH2 p.Asn417= (c.1251C>T) is classified Likely benign in CDH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-21). Ultra-rare (popmax 0.066%, mid); Associated with Inborn genetic diseases.

What condition is associated with CDH2 p.Asn417= (c.1251C>T)?

CDH2 p.Asn417= (c.1251C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDH2 p.Asn417= (c.1251C>T) in the general population?

CDH2 p.Asn417= (c.1251C>T) is ultra-rare (popmax 0.066%, mid) (gnomAD).

CDH2 p.Asn417=

c.1251C>T · rs138990743 · VCV757117

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -5.6
Overall
CADD	6.082	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00694% 112/1,613,902 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.128%	779
Middle Easterngrpmax	0.066%	1,516
African / African-American	0.0213%	4,690
Remaining individualsnot grpmax-eligible	0.0112%	8,928
East Asian	0.00446%	22,429
European (non-Finnish)	0.00348%	28,776
Admixed American	0.00333%	30,010
Finnishnot grpmax-eligible	0.00312%	32,018

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn417=
Coding: c.1251C>T
MANE Select: NM_001792
dbSNP: rs138990743
Type: single nucleotide variant
Location: chr18:27992748 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 417: 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.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-asn417 (accessed [today's date]).

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