Is CDH3 p.Arg747Gln (c.2240G>A) pathogenic?

CDH3 p.Arg747Gln (c.2240G>A) is classified Uncertain significance in CDH3 (ClinVar, Single submitter, 2 submitters; last evaluated 2020-04-09). AlphaMissense: likely benign (0.2823); Ultra-rare (popmax 0.012%, afr); Associated with inherited retinal dystrophy.

What condition is associated with CDH3 p.Arg747Gln (c.2240G>A)?

CDH3 p.Arg747Gln (c.2240G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is CDH3 p.Arg747Gln (c.2240G>A) in the general population?

CDH3 p.Arg747Gln (c.2240G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about CDH3 p.Arg747Gln (c.2240G>A)?

AlphaMissense predicts likely benign (score 0.2823) — an in-silico prediction, not a clinical call.

CDH3 p.Arg747Gln

c.2240G>A · rs772291014 · VCV1008783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2823 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.2823	likely benign
REVEL	0.556	indeterminate
SaProt	LLR -9.45	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 12	GERP 2.1, phastCons 1
Overall
CADD	31.0	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 0.012% African / African-American · 9/74,870 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00149% 24/1,613,944 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,319
Admixed American	0.00167%	59,984
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.0011%	90,773

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: CDH3
Protein: p.Arg747Gln
Coding: c.2240G>A
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs772291014
Type: single nucleotide variant
Location: chr16:68695883 (GRCh38)
Structure: AlphaFold pLDDT 78.70

Full CDH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH3 p.Arg747= Benign ★★ same residue
CDH3 p.Arg747Leu Uncertain significance ★ ⚠ same residue
CDH3 p.Arg747Trp Uncertain significance ★ ⚠ same residue
CDH3 p.Arg503His Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDH3 p.Trp362Ter Pathogenic ★★ same condition
CDH3 p.Ala150Thr Uncertain significance ★★ ⚠ same condition
CDH3 p.Arg681Trp Uncertain significance ★★ ⚠ same condition
CDH3 p.Arg731Cys 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-arg747gln (accessed [today's date]).

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