Is CDH7 p.Arg683Trp (c.2047C>T) pathogenic?

CDH7 p.Arg683Trp (c.2047C>T) is classified Uncertain significance in CDH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: ambiguous (0.4813); Very rare (popmax 0.0022%, sas).

How common is CDH7 p.Arg683Trp (c.2047C>T) in the general population?

CDH7 p.Arg683Trp (c.2047C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CDH7 p.Arg683Trp (c.2047C>T)?

AlphaMissense predicts ambiguous (score 0.4813) — an in-silico prediction, not a clinical call.

CDH7 p.Arg683Trp

c.2047C>T · VCV4223982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4813 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4813	ambiguous
REVEL	0.843	moderately pathogenic-leaning
SaProt	LLR -10.24	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.8, phastCons 0.99
Overall
CADD	26.4	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

Grpmax group 0.0022% South Asian · 2/91,030 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000342% 5/1,461,696 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,515
Admixed American	0.00167%	59,946
European (non-Finnish)	0.00017%	589,957

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDH7
Protein: p.Arg683Trp
Coding: c.2047C>T
MANE Select: NM_021153 · reported on NM_004361
Type: single nucleotide variant
Location: chr18:65880583 (GRCh38)
Structure: AlphaFold pLDDT 78.14

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

Similar variants

CDH19 p.Arg683Gly 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
CDH7 c.210+52G>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/cdh7-p-arg683trp (accessed [today's date]).

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