Is CDH11 p.Asp596Tyr (c.1786G>T) pathogenic?

CDH11 p.Asp596Tyr (c.1786G>T) is classified Uncertain significance in CDH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: ambiguous (0.4605); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDH11 p.Asp596Tyr (c.1786G>T)?

CDH11 p.Asp596Tyr (c.1786G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDH11 p.Asp596Tyr (c.1786G>T) in the general population?

CDH11 p.Asp596Tyr (c.1786G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CDH11 p.Asp596Tyr (c.1786G>T)?

AlphaMissense predicts ambiguous (score 0.4605) — an in-silico prediction, not a clinical call.

CDH11 p.Asp596Tyr

c.1786G>T · rs374274441 · VCV2602001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4605 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4605	ambiguous
REVEL	0.542	indeterminate
SaProt	LLR -16.40	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 44 kb · p 0.01 · regional, not allelic
Overall
CADD	26.0	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 0.00167% Admixed American · 1/60,010 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,614,100 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,010
European (non-Finnish)	0.000678%	147,507

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: CDH11
Protein: p.Asp596Tyr
Coding: c.1786G>T
MANE Select: NM_001797
dbSNP: rs374274441
Type: single nucleotide variant
Location: chr16:64950875 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 596: the cadherin 5 domain; a UniProt-annotated variant site (in esws)

Full CDH11 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

CDH11 p.Ala228Ser Uncertain significance ★★ ⚠ same condition
CDH11 p.Arg556Trp Uncertain significance ★★ ⚠ same condition
CDH11 p.Gly45Arg Uncertain significance ★★ ⚠ same condition
CDH11 p.Gly618Ser Uncertain significance ★★ ⚠ same condition
CDH11 p.Ile649Val Uncertain significance ★★ ⚠ same condition
CDH11 p.Val478Ile Likely benign ★★ same condition
CDH11 p.Ala470Val Uncertain significance ★ ⚠ same condition
CDH11 p.Ala475Thr 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/cdh11-p-asp596tyr (accessed [today's date]).

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