Is CDH11 p.Pro525Arg (c.1574C>G) pathogenic?

CDH11 p.Pro525Arg (c.1574C>G) is classified Uncertain significance in CDH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-27). AlphaMissense: ambiguous (0.3765); Absent from gnomAD v4.1.

How common is CDH11 p.Pro525Arg (c.1574C>G) in the general population?

CDH11 p.Pro525Arg (c.1574C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH11 p.Pro525Arg (c.1574C>G)?

AlphaMissense predicts ambiguous (score 0.3765) — an in-silico prediction, not a clinical call.

CDH11 p.Pro525Arg

c.1574C>G · VCV4853661

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3765 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3765	ambiguous
REVEL	0.152	moderately benign-leaning
SaProt	LLR -7.95	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.54, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 44 kb · p 0.01 · regional, not allelic
Overall
CADD	22.3	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: CDH11
Protein: p.Pro525Arg
Coding: c.1574C>G
MANE Select: NM_001797
Type: single nucleotide variant
Location: chr16:64971647 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 525: 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

Similar variants

CDH11 p.Pro525Gln Uncertain significance ★ ⚠ same residue
CDH11 p.Asp260Asn Pathogenic/Likely pathogenic ★★ same type
CDH11 p.Ala228Ser Uncertain significance ★★ ⚠ same type
CDH11 p.Arg556Trp Uncertain significance ★★ ⚠ same type
CDH11 p.Asp718Asn Uncertain significance ★★ ⚠ same type
CDH11 p.Gly45Arg Uncertain significance ★★ ⚠ same type
CDH11 p.Gly618Ser Uncertain significance ★★ ⚠ same type
CDH11 p.Ile649Val Uncertain significance ★★ ⚠ 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/cdh11-p-pro525arg (accessed [today's date]).

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