Is CDH2 p.Glu672Asp (c.2016A>T) pathogenic?

CDH2 p.Glu672Asp (c.2016A>T) is classified Conflicting classifications of pathogenicity in CDH2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.1159); Ultra-rare (popmax 0.0883%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDH2 p.Glu672Asp (c.2016A>T)?

CDH2 p.Glu672Asp (c.2016A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDH2 p.Glu672Asp (c.2016A>T) in the general population?

CDH2 p.Glu672Asp (c.2016A>T) is ultra-rare (popmax 0.0883%, amr) (gnomAD).

What do computational predictors say about CDH2 p.Glu672Asp (c.2016A>T)?

AlphaMissense predicts likely benign (score 0.1159) — an in-silico prediction, not a clinical call.

CDH2 p.Glu672Asp

c.2016A>T · rs151218256 · VCV1386296

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1159 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0883%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1159	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -6.80	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 0.55	GERP -5.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 27 kb · p 4e-09 · regional, not allelic
Overall
CADD	15.24	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 0.0883% Admixed American · 53/60,018 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0625%

Overall 0.0199% 321/1,612,842 alleles · ultra-rare exomes 278/1,460,540 · genomes 43/152,302 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0883%	1,132
Middle Eastern	0.0495%	2,020
Ashkenazi Jewishnot grpmax-eligible	0.0406%	2,466
Remaining individualsnot grpmax-eligible	0.0224%	4,461
European (non-Finnish)	0.0196%	5,103
South Asian	0.00659%	15,175
Finnishnot grpmax-eligible	0.00312%	32,010

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.Glu672Asp
Coding: c.2016A>T
MANE Select: NM_001792
dbSNP: rs151218256
Type: single nucleotide variant
Location: chr18:27985193 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 672: the cadherin 5 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-glu672asp (accessed [today's date]).

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