Is CDH13 p.Pro583= (c.1749G>T) pathogenic?

CDH13 p.Pro583= (c.1749G>T) is classified Likely benign in CDH13 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-03). Very rare (popmax 0.000509%, nfe); Associated with CDH13-related disorder.

What condition is associated with CDH13 p.Pro583= (c.1749G>T)?

CDH13 p.Pro583= (c.1749G>T) is associated with CDH13-related disorder (ClinVar).

How common is CDH13 p.Pro583= (c.1749G>T) in the general population?

CDH13 p.Pro583= (c.1749G>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

CDH13 p.Pro583=

c.1749G>T · rs541617175 · VCV3043561

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

CDH13-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.30	acceptor gain · deltas
Pangolin	Δ0.20	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.24	GERP -5.5, phastCons 0.001
Overall
CADD	14.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,880 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,806 alleles · very rare

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: CDH13
Protein: p.Pro583=
Coding: c.1749G>T
MANE Select: NM_001257
dbSNP: rs541617175
Type: single nucleotide variant
Location: chr16:83780035 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.19 · 1 PDB
Residue 583: the cadherin 4 domain

Full CDH13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CDH13-related disorder

Similar variants

CDH13 p.Ile585Val Uncertain significance ★ ⚠ same condition
CDH13 p.Lys293Gln Uncertain significance ⚠ same condition
CDH13 c.45+12327A>G Benign same condition
CDH13 c.45+8A>G Likely benign same condition
CDH13 c.781+4T>A Likely benign same condition
CDH13 p.Asn420= Likely benign same condition
CDH13 p.Asp577= Likely benign same condition
CDH13 p.Gly261= 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/cdh13-p-pro583 (accessed [today's date]).

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