Is CDH11 p.Val272Ile (c.814G>A) pathogenic?

CDH11 p.Val272Ile (c.814G>A) is classified Uncertain significance in CDH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). AlphaMissense: likely benign (0.0726); Ultra-rare (popmax 0.0501%, mid); Associated with Inborn genetic diseases.

What condition is associated with CDH11 p.Val272Ile (c.814G>A)?

CDH11 p.Val272Ile (c.814G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDH11 p.Val272Ile (c.814G>A) in the general population?

CDH11 p.Val272Ile (c.814G>A) is ultra-rare (popmax 0.0501%, mid) (gnomAD).

What do computational predictors say about CDH11 p.Val272Ile (c.814G>A)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

CDH11 p.Val272Ile

c.814G>A · VCV3488703

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0501%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 44 kb · p 0.01 · regional, not allelic
Overall
CADD	22.8	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 0.0501% Middle Eastern · 3/5,986 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00727%

Overall 0.00262% 42/1,602,480 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0501%	1,995
South Asian	0.00902%	11,087
Admixed American	0.00522%	19,154
African / African-American	0.0027%	37,069
East Asian	0.00224%	44,668
European (non-Finnish)	0.00204%	48,997
Remaining individualsnot grpmax-eligible	0.00162%	61,900

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.Val272Ile
Coding: c.814G>A
MANE Select: NM_001797
Type: single nucleotide variant
Location: chr16:64988342 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 272: a UniProt-annotated variant site (in esws); 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.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-val272ile (accessed [today's date]).

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