Is CDH3 p.Pro26= (c.78G>C) pathogenic?

CDH3 p.Pro26= (c.78G>C) is classified Likely benign in CDH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-22). Ultra-rare (popmax 0.0202%, sas).

How common is CDH3 p.Pro26= (c.78G>C) in the general population?

CDH3 p.Pro26= (c.78G>C) is ultra-rare (popmax 0.0202%, sas) (gnomAD).

CDH3 p.Pro26=

c.78G>C · rs992399939 · VCV1973140

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.84	GERP -2.6
Overall
CADD	10.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0202% South Asian · 17/83,976 alleles

Filtering AF 0.0129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0105%

Overall 0.00122% 17/1,392,116 alleles · ultra-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.Pro26=
Coding: c.78G>C
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs992399939
Type: single nucleotide variant
Location: chr16:68645668 (GRCh38)
Structure: AlphaFold pLDDT 78.70

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

Similar variants

CDH3 p.Pro26Leu Uncertain significance ★★ ⚠ same residue
CDH15 p.Arg26Lys Uncertain significance ★ ⚠ same residue
CDH3 p.Pro26Arg Uncertain significance ★ ⚠ same residue
CDH15 p.Arg26= Likely benign ★ same residue
CDH3 c.1796-2A>G Pathogenic ★★ same type
CDH3 c.691+1G>A Pathogenic/Likely pathogenic ★★ same type
CDH3 p.Arg103Ter Pathogenic ★★ same type
CDH3 p.Arg221Ter 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-pro26 (accessed [today's date]).

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