Is CDH11 p.Phe690Leu (c.2068T>C) pathogenic?

CDH11 p.Phe690Leu (c.2068T>C) is classified Uncertain significance in CDH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely pathogenic (0.9051); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDH11 p.Phe690Leu (c.2068T>C)?

CDH11 p.Phe690Leu (c.2068T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CDH11 p.Phe690Leu (c.2068T>C) in the general population?

CDH11 p.Phe690Leu (c.2068T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH11 p.Phe690Leu (c.2068T>C)?

AlphaMissense predicts likely pathogenic (score 0.9051) — an in-silico prediction, not a clinical call.

CDH11 p.Phe690Leu

c.2068T>C · VCV4608690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9051 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9051	likely pathogenic
REVEL	0.141	moderately benign-leaning
SaProt	LLR -5.27	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 44 kb · p 0.01 · regional, not allelic
Overall
CADD	22.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDH11
Protein: p.Phe690Leu
Coding: c.2068T>C
MANE Select: NM_001797
Type: single nucleotide variant
Location: chr16:64947926 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 690: a UniProt-annotated variant site (in esws)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH11 p.Ala228Ser Uncertain significance ★★ ⚠ same condition
CDH11 p.Arg556Trp Uncertain significance ★★ ⚠ same condition
CDH11 p.Gly45Arg Uncertain significance ★★ ⚠ same condition
CDH11 p.Gly618Ser Uncertain significance ★★ ⚠ same condition
CDH11 p.Ile649Val Uncertain significance ★★ ⚠ same condition
CDH11 p.Val478Ile Likely benign ★★ same condition
CDH11 p.Ala470Val Uncertain significance ★ ⚠ same condition
CDH11 p.Ala475Thr 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/cdh11-p-phe690leu (accessed [today's date]).

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