Is CDH13 p.Ser69= (c.207G>A) pathogenic?

CDH13 p.Ser69= (c.207G>A) is classified Benign in CDH13 (ClinVar, Multiple submitters, 2 submitters). Common (popmax 57.1%, sas) — too common for a highly-penetrant pathogenic allele.

CDH13 p.Ser69=

Q: How common is CDH13 p.Ser69= (c.207G>A) in the general population?

CDH13 p.Ser69= (c.207G>A) is common (popmax 57.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.207G>A · rs6565105 · VCV257649

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 57.1%, sas) — 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 -0.38	GERP -3.4, phastCons 0.001
Overall
CADD	9.145	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 57.1% South Asian · 51,219/89,678 alleles

Filtering AF 56.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 56.5%

Overall 54.3% 873,255/1,607,566 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	64.4%	2
Finnishnot grpmax-eligible	62.9%	2
South Asiangrpmax	57.1%	2
European (non-Finnish)	54.5%	2
African / African-American	54%	2
Remaining individualsnot grpmax-eligible	53.2%	2
Admixed American	53.1%	2
Middle Eastern	46.5%	2
Ashkenazi Jewishnot grpmax-eligible	44.2%	2
East Asian	43.6%	2

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CDH13
Protein: p.Ser69=
Coding: c.207G>A
MANE Select: NM_001257
dbSNP: rs6565105
Type: single nucleotide variant
Location: chr16:83032059 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.19 · 1 PDB

Full CDH13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH13 p.Ser69Trp Uncertain significance ★ ⚠ same residue
CDH13 c.1102-6T>C Benign ★★ same type
CDH13 c.1284+90A>G Benign ★★ same type
CDH13 c.1539-109T>C Benign ★★ same type
CDH13 c.1681+64T>C Benign ★★ same type
CDH13 c.1682-151C>T Benign ★★ same type
CDH13 c.1682-180G>A Benign ★★ same type
CDH13 c.1682-59A>G Benign ★★ 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/cdh13-p-ser69 (accessed [today's date]).

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