Is CDH7 p.Arg547Thr (c.1640G>C) pathogenic?

CDH7 p.Arg547Thr (c.1640G>C) is classified Uncertain significance in CDH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). AlphaMissense: likely benign (0.3228); Ultra-rare (popmax 0.0266%, nfe).

How common is CDH7 p.Arg547Thr (c.1640G>C) in the general population?

CDH7 p.Arg547Thr (c.1640G>C) is ultra-rare (popmax 0.0266%, nfe) (gnomAD).

What do computational predictors say about CDH7 p.Arg547Thr (c.1640G>C)?

AlphaMissense predicts likely benign (score 0.3228) — an in-silico prediction, not a clinical call.

CDH7 p.Arg547Thr

c.1640G>C · rs140905426 · VCV2515425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3228 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0266%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3228	likely benign
REVEL	0.58	indeterminate
SaProt	LLR -7.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.4, phastCons 1
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0266% European (non-Finnish) · 314/1,180,014 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0232%

Overall 0.02% 322/1,614,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0266%	3,758
Remaining individualsnot grpmax-eligible	0.0128%	7,811

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.Arg547Thr
Coding: c.1640G>C
MANE Select: NM_021153 · reported on NM_004361
dbSNP: rs140905426
Type: single nucleotide variant
Location: chr18:65862693 (GRCh38)
Structure: AlphaFold pLDDT 78.14
Residue 547: the cadherin 5 domain

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

Similar variants

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
CDH7 c.210+56T>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-arg547thr (accessed [today's date]).

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