Is CDH7 p.Ser752Arg (c.2256C>G) pathogenic?

CDH7 p.Ser752Arg (c.2256C>G) is classified Uncertain significance in CDH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely pathogenic (0.7099); Ultra-rare (popmax 0.0549%, nfe).

How common is CDH7 p.Ser752Arg (c.2256C>G) in the general population?

CDH7 p.Ser752Arg (c.2256C>G) is ultra-rare (popmax 0.0549%, nfe) (gnomAD).

What do computational predictors say about CDH7 p.Ser752Arg (c.2256C>G)?

AlphaMissense predicts likely pathogenic (score 0.7099) — an in-silico prediction, not a clinical call.

CDH7 p.Ser752Arg

c.2256C>G · rs147379460 · VCV2347837

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7099 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7099	likely pathogenic
REVEL	0.573	indeterminate
SaProt	LLR -10.89	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 0.42	GERP 0.65, phastCons 0.99
Overall
CADD	20.5	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

Grpmax group 0.0549% European (non-Finnish) · 648/1,180,004 alleles

Filtering AF 0.0513% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.05%

Overall 0.0424% 684/1,614,000 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0549%	1,821
Remaining individualsnot grpmax-eligible	0.0224%	4,463
Finnishnot grpmax-eligible	0.0156%	6,403
African / African-American	0.0133%	7,492
Admixed American	0.00333%	30,003

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.Ser752Arg
Coding: c.2256C>G
MANE Select: NM_021153 · reported on NM_004361
dbSNP: rs147379460
Type: single nucleotide variant
Location: chr18:65880792 (GRCh38)
Structure: AlphaFold pLDDT 78.14

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

Similar variants

CDH19 p.Glu752Lys 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-ser752arg (accessed [today's date]).

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