Is CDH3 p.Val75fs (c.222del) pathogenic?

CDH3 p.Val75fs (c.222del) is classified Pathogenic in CDH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-29). Very rare (popmax 0.005%, amr).

How common is CDH3 p.Val75fs (c.222del) in the general population?

CDH3 p.Val75fs (c.222del) is very rare (popmax 0.005%, amr) (gnomAD).

CDH3 p.Val75fs

c.222del · rs767009501 · VCV2055956

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.081	GERP -4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,026 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000205% 3/1,461,484 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: CDH3
Protein: p.Val75fs
Coding: c.222del
MANE Select: NM_001793
dbSNP: rs767009501
Type: Deletion
Location: chr16:68676446 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.71 · 19 PDB

Full CDH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH3 p.Gly277fs Pathogenic ★★ same type
CDH3 p.Lys106fs Pathogenic ★★ same type
CDH3 p.Lys401fs Pathogenic/Likely pathogenic ★★ same type
CDH3 c.391-7_391-3del Uncertain significance ★★ same type
CDH3 p.Ser791_Leu792insTer Uncertain significance ★★ same type
CDH3 c.2133+14_2133+22del Benign/Likely benign ★★ same type
CDH3 p.Asp372fs Pathogenic ★ same type
CDH3 p.Asp696fs Likely pathogenic ★ same type

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/cdh3-p-val75fs (accessed [today's date]).

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