Is CDH11 p.Arg28Gln (c.83G>A) pathogenic?

CDH11 p.Arg28Gln (c.83G>A) is classified Uncertain significance in CDH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely benign (0.0726); Ultra-rare (popmax 0.0514%, amr).

How common is CDH11 p.Arg28Gln (c.83G>A) in the general population?

CDH11 p.Arg28Gln (c.83G>A) is ultra-rare (popmax 0.0514%, amr) (gnomAD).

What do computational predictors say about CDH11 p.Arg28Gln (c.83G>A)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

CDH11 p.Arg28Gln

c.83G>A · rs527451513 · VCV2502759

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0514%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.4, phastCons 0.11
Regional constraint	o/e 0.67	unconstrained · MANE · 13 kb · p 3.9e-10 · regional, not allelic
Overall
CADD	19.25	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 0.0514% Admixed American · 30/58,350 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0321%

Overall 0.00699% 112/1,601,336 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0514%	1,945
Remaining individualsnot grpmax-eligible	0.0113%	8,860
East Asian	0.00911%	10,974
South Asian	0.00896%	11,165
African / African-American	0.00804%	12,433
European (non-Finnish)	0.00477%	20,966
Finnishnot grpmax-eligible	0.00159%	62,966

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: CDH11
Protein: p.Arg28Gln
Coding: c.83G>A
MANE Select: NM_001797
dbSNP: rs527451513
Type: single nucleotide variant
Location: chr16:65004787 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65

Full CDH11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH11 p.Arg28Trp Uncertain significance ★ ⚠ same residue
CDH11 p.Asp260Asn Pathogenic/Likely pathogenic ★★ same type
CDH11 p.Ala228Ser Uncertain significance ★★ ⚠ same type
CDH11 p.Arg556Trp Uncertain significance ★★ ⚠ same type
CDH11 p.Asp718Asn Uncertain significance ★★ ⚠ same type
CDH11 p.Gly45Arg Uncertain significance ★★ ⚠ same type
CDH11 p.Gly618Ser Uncertain significance ★★ ⚠ same type
CDH11 p.Ile649Val Uncertain significance ★★ ⚠ 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/cdh11-p-arg28gln (accessed [today's date]).

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