Is CDH13 p.Asp453= (c.1359C>T) pathogenic?

CDH13 p.Asp453= (c.1359C>T) is classified Benign in CDH13 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-06-10). Common (popmax 13.2%, afr) — too common for a highly-penetrant pathogenic allele.

CDH13 p.Asp453=

Q: How common is CDH13 p.Asp453= (c.1359C>T) in the general population?

CDH13 p.Asp453= (c.1359C>T) is common (popmax 13.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1359C>T · rs34697339 · VCV257643

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 13.2%, 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 -14	GERP -4.1
Overall
CADD	0.096	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.2% African / African-American · 9,878/74,974 alleles

Filtering AF 13% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.9%

Overall 3.96% 63,853/1,613,856 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.2%	8
Finnishnot grpmax-eligible	7.98%	13
South Asian	4.73%	21
Ashkenazi Jewishnot grpmax-eligible	4.21%	24
Remaining individualsnot grpmax-eligible	3.88%	26
Middle Eastern	3.35%	30
European (non-Finnish)	3.3%	30
Amishnot grpmax-eligible	3.08%	33
Admixed American	2.85%	35
East Asian	0.14%	712

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.Asp453=
Coding: c.1359C>T
MANE Select: NM_001257
dbSNP: rs34697339
Type: single nucleotide variant
Location: chr16:83678282 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.19 · 1 PDB
Residue 453: the cadherin 3 domain

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

Similar variants

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
CDH13 c.1682-62G>A 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-asp453 (accessed [today's date]).

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