Is CDH2 p.Val162Asp (c.485T>A) pathogenic?

CDH2 p.Val162Asp (c.485T>A) is classified Pathogenic in CDH2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2008-10-15). AlphaMissense: likely pathogenic (0.9889); Absent from gnomAD v4.1; Associated with agenesis of corpus callosum, cardiac, ocular, and genital syndrome.

What condition is associated with CDH2 p.Val162Asp (c.485T>A)?

CDH2 p.Val162Asp (c.485T>A) is associated with agenesis of corpus callosum, cardiac, ocular, and genital syndrome (ClinVar).

How common is CDH2 p.Val162Asp (c.485T>A) in the general population?

CDH2 p.Val162Asp (c.485T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH2 p.Val162Asp (c.485T>A)?

AlphaMissense predicts likely pathogenic (score 0.9889) — an in-silico prediction, not a clinical call.

CDH2 p.Val162Asp

c.485T>A · rs2013111940 · VCV929855

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9889 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

agenesis of corpus callosum, cardiac, ocular, and genital syndrome

Computational evidence

Protein change
AlphaMissense	0.9889	likely pathogenic ✓ concordant with ClinVar
REVEL	0.733	pathogenic-leaning
SaProt	LLR -12.44	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	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	28.6	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.Val162Asp
Coding: c.485T>A
MANE Select: NM_001792
dbSNP: rs2013111940
Type: single nucleotide variant
Location: chr18:28011907 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 162: a UniProt-annotated variant site (in acogs; uncertain significance); the cadherin 1 domain

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

Disease context

agenesis of corpus callosum, cardiac, ocular, and genital syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH2 c.1344+1G>A Pathogenic/Likely pathogenic ★★ same condition
CDH2 c.702+1G>A Pathogenic/Likely pathogenic ★★ same condition
CDH2 p.Tyr676Cys Pathogenic ★★ same condition
CDH2 c.848-16T>G Uncertain significance ★★ same condition
CDH2 p.Phe835Leu Uncertain significance ★★ ⚠ same condition
CDH2 p.Val566Met Uncertain significance ★★ ⚠ same condition
CDH2 c.702+6A>T Benign/Likely benign ★★ same condition
CDH2 p.Asp295= Benign/Likely benign ★★ 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-val162asp (accessed [today's date]).

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