Is CDH2 p.Cys613Trp (c.1839C>G) pathogenic?

CDH2 p.Cys613Trp (c.1839C>G) is classified Pathogenic in CDH2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-26). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1; Associated with corpus callosum, agenesis of.

What condition is associated with CDH2 p.Cys613Trp (c.1839C>G)?

CDH2 p.Cys613Trp (c.1839C>G) is associated with corpus callosum, agenesis of (ClinVar).

How common is CDH2 p.Cys613Trp (c.1839C>G) in the general population?

CDH2 p.Cys613Trp (c.1839C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH2 p.Cys613Trp (c.1839C>G)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

CDH2 p.Cys613Trp

c.1839C>G · rs754880999 · VCV805762

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

corpus callosum, agenesis of

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic ✓ concordant with ClinVar · top 3% in CDH2
REVEL	0.507	indeterminate
SaProt	LLR -17.03	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -5.6
Regional constraint	o/e 0.78	unconstrained · MANE · 27 kb · p 4e-09 · regional, not allelic
Overall
CADD	12.91	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.Cys613Trp
Coding: c.1839C>G
MANE Select: NM_001792
dbSNP: rs754880999
Type: single nucleotide variant
Location: chr18:27985664 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 613: the cadherin 5 domain; a UniProt-annotated variant site (in acogs; decreased function in cell-cell adhesion)

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

Disease context

corpus callosum, agenesis of — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH2 p.Cys613= Likely benign ★★ same residue
CDH2 p.Tyr676Cys Pathogenic ★★ same condition
CDH2 p.Asp353Asn Likely pathogenic ★ same condition
CDH2 p.Asn601Thr Pathogenic same condition
CDH2 p.Asp597Asn Pathogenic/Likely pathogenic same condition
CDH2 p.Asp597Tyr Pathogenic same condition
CDH2 p.Asp627Gly Pathogenic/Likely pathogenic same condition
CDH2 p.Leu856fs Likely pathogenic ★ 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-cys613trp (accessed [today's date]).

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