Is CDH20 p.Pro39= (c.117A>G) pathogenic?

CDH20 p.Pro39= (c.117A>G) is classified Benign in CDH20 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-02). Common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele.

CDH20 p.Pro39=

Q: How common is CDH20 p.Pro39= (c.117A>G) in the general population?

CDH20 p.Pro39= (c.117A>G) is common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.117A>G · rs34813888 · VCV710667

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele

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 -7.5	GERP -2.9
Overall
CADD	0.069	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.56% African / African-American · 4,917/74,990 alleles

Filtering AF 6.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.34%

Overall 0.352% 5,679/1,614,052 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.56%	15
Admixed American	0.532%	188
Remaining individualsnot grpmax-eligible	0.498%	201
Middle Eastern	0.214%	466
South Asian	0.0198%	5,060
European (non-Finnish)	0.00856%	11,683

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: CDH20
Protein: p.Pro39=
Coding: c.117A>G
MANE Select: NM_031891
dbSNP: rs34813888
Type: single nucleotide variant
Location: chr18:61490670 (GRCh38)
Gene constraint: LOEUF 0.532 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 77.33

Full CDH20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH20 p.Arg687Trp Uncertain significance ★★ ⚠ same type
CDH20 p.Ala226Val Uncertain significance ★ same type
CDH20 p.Ala403Val Uncertain significance ★ ⚠ same type
CDH20 p.Ala506Thr Uncertain significance ★ ⚠ same type
CDH20 p.Ala610Val Uncertain significance ★ ⚠ same type
CDH20 p.Ala627Thr Uncertain significance ★ ⚠ same type
CDH20 p.Ala691Thr Uncertain significance ★ ⚠ same type
CDH20 p.Ala717Thr 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/cdh20-p-pro39 (accessed [today's date]).

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