Is CDH1 p.Pro513Arg (c.1538C>G) pathogenic?

CDH1 p.Pro513Arg (c.1538C>G) is classified Uncertain significance in CDH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-22). AlphaMissense: ambiguous (0.4444); Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with CDH1 p.Pro513Arg (c.1538C>G)?

CDH1 p.Pro513Arg (c.1538C>G) is associated with hereditary breast carcinoma (ClinVar).

How common is CDH1 p.Pro513Arg (c.1538C>G) in the general population?

CDH1 p.Pro513Arg (c.1538C>G) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CDH1 p.Pro513Arg (c.1538C>G)?

AlphaMissense predicts ambiguous (score 0.4444) — an in-silico prediction, not a clinical call.

CDH1 p.Pro513Arg

c.1538C>G · rs1555516185 · VCV2680440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4444 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.4444	ambiguous
REVEL	0.548	indeterminate
SaProt	LLR -8.11	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 25 kb · p 0.00015 · regional, not allelic
Overall
CADD	26.6	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: CDH1
Protein: p.Pro513Arg
Coding: c.1538C>G
MANE Select: NM_004360
dbSNP: rs1555516185
Type: single nucleotide variant
Location: chr16:68815732 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 513: the cadherin 4 domain

Full CDH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

CDH1 p.Pro513Leu Uncertain significance ★★ ⚠ same residue
CDH1 p.Pro513Thr Uncertain significance ★★ same residue
CDH1 c.1137+1G>A Pathogenic ★★★ same condition
CDH1 c.1565+1G>A Pathogenic ★★★ same condition
CDH1 c.1565+1G>T Pathogenic ★★★ same condition
CDH1 c.2165-1G>C Likely pathogenic ★★★ same condition
CDH1 c.49-2A>G Pathogenic ★★★ same condition
CDH1 c.532-1G>C 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/cdh1-p-pro513arg (accessed [today's date]).

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