Is CDH11 p.Val234Met (c.700G>A) pathogenic?

CDH11 p.Val234Met (c.700G>A) is classified Uncertain significance in CDH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). AlphaMissense: likely pathogenic (0.7542); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with CDH11 p.Val234Met (c.700G>A)?

CDH11 p.Val234Met (c.700G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDH11 p.Val234Met (c.700G>A) in the general population?

CDH11 p.Val234Met (c.700G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CDH11 p.Val234Met (c.700G>A)?

AlphaMissense predicts likely pathogenic (score 0.7542) — an in-silico prediction, not a clinical call.

CDH11 p.Val234Met

c.700G>A · VCV3488709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7542 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7542	likely pathogenic
REVEL	0.36	indeterminate
SaProt	LLR -11.47	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 13 kb · p 3.9e-10 · regional, not allelic
Overall
CADD	33.0	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 0.0022% South Asian · 2/91,066 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000682% 11/1,613,872 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,533
Admixed American	0.00167%	60,018
European (non-Finnish)	0.000678%	147,473

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.Val234Met
Coding: c.700G>A
MANE Select: NM_001797
Type: single nucleotide variant
Location: chr16:64991879 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 234: a UniProt-annotated variant site (in esws); the cadherin 2 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.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-val234met (accessed [today's date]).

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