Is CDH7 p.Arg47Cys (c.139C>T) pathogenic?

CDH7 p.Arg47Cys (c.139C>T) is classified Uncertain significance in CDH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-30). AlphaMissense: likely pathogenic (0.9721); Absent from gnomAD v4.1.

How common is CDH7 p.Arg47Cys (c.139C>T) in the general population?

CDH7 p.Arg47Cys (c.139C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH7 p.Arg47Cys (c.139C>T)?

AlphaMissense predicts likely pathogenic (score 0.9721) — an in-silico prediction, not a clinical call.

CDH7 p.Arg47Cys

c.139C>T · VCV3830215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9721 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9721	likely pathogenic · top 2% in CDH7
REVEL	0.398	indeterminate
SaProt	LLR -12.27	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: CDH7
Protein: p.Arg47Cys
Coding: c.139C>T
MANE Select: NM_021153 · reported on NM_004361
Type: single nucleotide variant
Location: chr18:65762981 (GRCh38)
Structure: AlphaFold pLDDT 78.14
Residue 47: the cadherin 1 domain

Full CDH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH19 p.Trp47Cys Uncertain significance ★ ⚠ same residue
CDH7 p.Arg47His Uncertain significance ★ ⚠ same residue
CDH19 p.Pro558= Benign ★★ same type
CDH19 p.Thr89Ile Benign ★★ same type
CDH7 c.1612+22C>T Benign ★★ same type
CDH7 c.1612+24A>T Benign ★★ same type
CDH7 c.1612+81T>C Benign ★★ same type
CDH7 c.1864+225A>G 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/cdh7-p-arg47cys (accessed [today's date]).

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