Is CDH3 p.Pro578Thr (c.1732C>A) pathogenic?

CDH3 p.Pro578Thr (c.1732C>A) is classified Uncertain significance in CDH3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-30). AlphaMissense: likely benign (0.2111); No allele count reported in gnomAD v4.1 (AN 1,614,112); Associated with Inborn genetic diseases.

What condition is associated with CDH3 p.Pro578Thr (c.1732C>A)?

CDH3 p.Pro578Thr (c.1732C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDH3 p.Pro578Thr (c.1732C>A) in the general population?

CDH3 p.Pro578Thr (c.1732C>A) is no allele count reported in gnomAD v4.1 (AN 1,614,112) (gnomAD).

What do computational predictors say about CDH3 p.Pro578Thr (c.1732C>A)?

AlphaMissense predicts likely benign (score 0.2111) — an in-silico prediction, not a clinical call.

CDH3 p.Pro578Thr

c.1732C>A · VCV4609713

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2111 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,112)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2111	likely benign
REVEL	0.357	indeterminate
SaProt	LLR -12.89	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.2, phastCons 1
Overall
CADD	23.5	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

No allele count reported in gnomAD v4.1 (AN 1,614,112). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDH3
Protein: p.Pro578Thr
Coding: c.1732C>A
MANE Select: NM_001793
Type: single nucleotide variant
Location: chr16:68687673 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.71 · 19 PDB
Residue 578: the cadherin 5 domain

Full CDH3 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

CDH3 p.Ala150Thr Uncertain significance ★★ same condition
CDH3 p.Ala22Glu Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala356Pro Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala361Ser Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala361Val Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala64Ser Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala724Ser Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala749Ser 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/cdh3-p-pro578thr (accessed [today's date]).

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