Is CDH3 p.Thr310fs (c.927dup) pathogenic?

CDH3 p.Thr310fs (c.927dup) is classified Pathogenic in CDH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-09). Very rare (popmax 0.00134%, afr).

How common is CDH3 p.Thr310fs (c.927dup) in the general population?

CDH3 p.Thr310fs (c.927dup) is very rare (popmax 0.00134%, afr) (gnomAD).

CDH3 p.Thr310fs

c.927dup · rs1384363306 · VCV2050951

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP -1.4
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,904 alleles

Overall 0.000657% 1/152,114 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.Thr310fs
Coding: c.927dup
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs1384363306
Type: Duplication
Location: chr16:68681025 (GRCh38)
Structure: AlphaFold pLDDT 78.70
Residue 310: the cadherin 3 domain

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

Similar variants

CDH3 p.Thr310= Likely benign ★ same residue
CDH3 p.Asp613fs Pathogenic ★★ same type
CDH3 c.2280+1dup Likely pathogenic ★ same type
CDH3 p.Ala40fs Pathogenic ★ same type
CDH3 p.Leu687fs Pathogenic ★ same type
CDH15 p.Asn531fs Uncertain significance ★ same type
CDH15 p.Thr600fs Uncertain significance ★ same type
CDH15 p.Val340fs Uncertain significance ★ 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-thr310fs (accessed [today's date]).

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