Is CDH11 p.Met275Arg (c.824T>G) pathogenic?

CDH11 p.Met275Arg (c.824T>G) is classified Uncertain significance in CDH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely pathogenic (0.735); Very rare (popmax 0.000509%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDH11 p.Met275Arg (c.824T>G)?

CDH11 p.Met275Arg (c.824T>G) is associated with Inborn genetic diseases (ClinVar).

How common is CDH11 p.Met275Arg (c.824T>G) in the general population?

CDH11 p.Met275Arg (c.824T>G) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about CDH11 p.Met275Arg (c.824T>G)?

AlphaMissense predicts likely pathogenic (score 0.735) — an in-silico prediction, not a clinical call.

CDH11 p.Met275Arg

c.824T>G · VCV3830017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.735	likely pathogenic
REVEL	0.61	indeterminate
SaProt	LLR -10.65	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
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	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000509% European (non-Finnish) · 6/1,179,254 alleles

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

Overall 0.000411% 6/1,460,312 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.Met275Arg
Coding: c.824T>G
MANE Select: NM_001797
Type: single nucleotide variant
Location: chr16:64988332 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 275: a UniProt-annotated variant site (in esws); a UniProt-annotated variant site (in); the cadherin 3 domain

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.Met275Ile Benign ★★ ⚠ same residue
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

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-met275arg (accessed [today's date]).

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