Is CDH1 p.Val51Phe (c.151G>T) pathogenic?

CDH1 p.Val51Phe (c.151G>T) is classified Uncertain significance in CDH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-19). AlphaMissense: likely benign (0.1242); No allele count reported in gnomAD v4.1 (AN 1,549,044); Associated with hereditary neoplastic syndrome.

What condition is associated with CDH1 p.Val51Phe (c.151G>T)?

CDH1 p.Val51Phe (c.151G>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDH1 p.Val51Phe (c.151G>T) in the general population?

CDH1 p.Val51Phe (c.151G>T) is no allele count reported in gnomAD v4.1 (AN 1,549,044) (gnomAD).

What do computational predictors say about CDH1 p.Val51Phe (c.151G>T)?

AlphaMissense predicts likely benign (score 0.1242) — an in-silico prediction, not a clinical call.

CDH1 p.Val51Phe

c.151G>T · VCV4632402

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1242 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,549,044)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1242	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -10.80	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP -2.7, phastCons 0.023
Regional constraint	o/e 1.05	unconstrained · MANE · 71 kb · p 0.52 · regional, not allelic
Overall
CADD	18.94	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

No allele count reported in gnomAD v4.1 (AN 1,549,044). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDH1
Protein: p.Val51Phe
Coding: c.151G>T
MANE Select: NM_004360
Type: single nucleotide variant
Location: chr16:68738399 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB

Full CDH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH1 p.Val51= Benign/Likely benign ★★ same residue
CDH1 p.Val51Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Val51Ala Uncertain significance ★ ⚠ same residue
CDH1 p.Val51Gly Uncertain significance ★ ⚠ same residue
CDH1 c.1008+2T>C Likely pathogenic ★★★ same condition
CDH1 c.1137+1G>A Pathogenic ★★★ same condition
CDH1 c.1137+2T>C Likely pathogenic ★★★ same condition
CDH1 c.1565+1G>A Pathogenic ★★★ 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/cdh1-p-val51phe (accessed [today's date]).

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