Is CDH3 p.Arg288Gln (c.863G>A) pathogenic?

CDH3 p.Arg288Gln (c.863G>A) is classified Uncertain significance in CDH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.2368); Ultra-rare (popmax 0.0164%, mid).

How common is CDH3 p.Arg288Gln (c.863G>A) in the general population?

CDH3 p.Arg288Gln (c.863G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CDH3 p.Arg288Gln (c.863G>A)?

AlphaMissense predicts likely benign (score 0.2368) — an in-silico prediction, not a clinical call.

CDH3 p.Arg288Gln

c.863G>A · rs371486773 · VCV1020476

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2368 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2368	likely benign
REVEL	0.604	indeterminate
SaProt	LLR -13.58	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.1, phastCons 1
Overall
CADD	33.0	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00347% 56/1,613,900 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0112%	8,924
African / African-American	0.00667%	14,988
European (non-Finnish)	0.00356%	28,093
South Asian	0.0011%	91,084

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.Arg288Gln
Coding: c.863G>A
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs371486773
Type: single nucleotide variant
Location: chr16:68679970 (GRCh38)
Structure: AlphaFold pLDDT 78.70
Residue 288: the cadherin 3 domain

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

Similar variants

CDH3 p.Arg288Trp Uncertain significance ★★ ⚠ same residue
CDH3 p.Arg288= Likely benign ★ same residue
CDH3 c.1796-2A>G Pathogenic ★★ same type
CDH3 c.691+1G>A Pathogenic/Likely pathogenic ★★ same type
CDH3 p.Arg103Ter Pathogenic ★★ same type
CDH3 p.Arg221Ter Pathogenic ★★ same type
CDH3 p.Arg503His Pathogenic/Likely pathogenic ★★ ⚠ same type
CDH3 p.Gln299Ter Pathogenic ★★ 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/cdh3-p-arg288gln (accessed [today's date]).

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