Is CDH13 p.Pro563Leu (c.1688C>T) pathogenic?

CDH13 p.Pro563Leu (c.1688C>T) is classified Uncertain significance in CDH13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-12). AlphaMissense: ambiguous (0.3744); Absent from gnomAD v4.1.

How common is CDH13 p.Pro563Leu (c.1688C>T) in the general population?

CDH13 p.Pro563Leu (c.1688C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH13 p.Pro563Leu (c.1688C>T)?

AlphaMissense predicts ambiguous (score 0.3744) — an in-silico prediction, not a clinical call.

CDH13 p.Pro563Leu

c.1688C>T · rs2508359739 · VCV2559536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3744	ambiguous
REVEL	0.478	indeterminate
SaProt	LLR -11.84	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.7, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 1,168 kb · p 1.2e-06 · regional, not allelic
Overall
CADD	27.9	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: CDH13
Protein: p.Pro563Leu
Coding: c.1688C>T
MANE Select: NM_001257
dbSNP: rs2508359739
Type: single nucleotide variant
Location: chr16:83779974 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.19 · 1 PDB
Residue 563: the cadherin 4 domain

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

Similar variants

CDH13 c.1102-6T>C Benign ★★ same type
CDH13 c.1284+90A>G Benign ★★ same type
CDH13 c.1539-109T>C Benign ★★ same type
CDH13 c.1681+64T>C Benign ★★ same type
CDH13 c.1682-151C>T Benign ★★ same type
CDH13 c.1682-180G>A Benign ★★ same type
CDH13 c.1682-59A>G Benign ★★ same type
CDH13 c.1682-62G>A Benign ★★ same type

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-pro563leu (accessed [today's date]).

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