Is CDH11 p.Thr587Ser (c.1760C>G) pathogenic?

CDH11 p.Thr587Ser (c.1760C>G) is classified Uncertain significance in CDH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-07). AlphaMissense: likely benign (0.2195); Very rare (popmax 0.000508%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDH11 p.Thr587Ser (c.1760C>G)?

CDH11 p.Thr587Ser (c.1760C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CDH11 p.Thr587Ser (c.1760C>G) in the general population?

CDH11 p.Thr587Ser (c.1760C>G) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about CDH11 p.Thr587Ser (c.1760C>G)?

AlphaMissense predicts likely benign (score 0.2195) — an in-silico prediction, not a clinical call.

CDH11 p.Thr587Ser

c.1760C>G · rs773287027 · VCV2299962

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2195 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2195	likely benign
REVEL	0.521	indeterminate
SaProt	LLR -9.15	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 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 44 kb · p 0.01 · regional, not allelic
Overall
CADD	28.4	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 0.000508% European (non-Finnish) · 6/1,180,030 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00041% 6/1,461,880 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.Thr587Ser
Coding: c.1760C>G
MANE Select: NM_001797
dbSNP: rs773287027
Type: single nucleotide variant
Location: chr16:64950901 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 587: the cadherin 5 domain; 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-thr587ser (accessed [today's date]).

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