Is CDH11 p.Lys694Glu (c.2080A>G) pathogenic?

CDH11 p.Lys694Glu (c.2080A>G) is classified Uncertain significance in CDH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: ambiguous (0.543); Very rare (popmax 0.000169%, nfe).

How common is CDH11 p.Lys694Glu (c.2080A>G) in the general population?

CDH11 p.Lys694Glu (c.2080A>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CDH11 p.Lys694Glu (c.2080A>G)?

AlphaMissense predicts ambiguous (score 0.543) — an in-silico prediction, not a clinical call.

CDH11 p.Lys694Glu

c.2080A>G · VCV4538904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.543 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
AlphaMissense	0.543	ambiguous
REVEL	0.491	indeterminate
SaProt	LLR -7.14	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 44 kb · p 0.01 · regional, not allelic
Overall
CADD	26.0	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 0.000169% European (non-Finnish) · 2/1,180,020 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,888 alleles · very rare

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.Lys694Glu
Coding: c.2080A>G
MANE Select: NM_001797
Type: single nucleotide variant
Location: chr16:64947914 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 694: a UniProt-annotated variant site (in esws)

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

Similar variants

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
CDH11 c.1253+43G>C 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/cdh11-p-lys694glu (accessed [today's date]).

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