Is CDH13 p.His253= (c.759C>T) pathogenic?

CDH13 p.His253= (c.759C>T) is classified Likely benign in CDH13 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-21). Ultra-rare (popmax 0.0983%, amr).

How common is CDH13 p.His253= (c.759C>T) in the general population?

CDH13 p.His253= (c.759C>T) is ultra-rare (popmax 0.0983%, amr) (gnomAD).

CDH13 p.His253=

c.759C>T · rs367662792 · VCV764610

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0983%, amr)

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 -13	GERP -3.7
Overall
CADD	1.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0983% Admixed American · 59/60,006 alleles

Filtering AF 0.0782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0709%

Overall 0.0044% 71/1,613,836 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0983%	1,017
African / African-American	0.004%	24,979
Finnishnot grpmax-eligible	0.00156%	64,018
European (non-Finnish)	0.000678%	147,479

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.His253=
Coding: c.759C>T
MANE Select: NM_001257
dbSNP: rs367662792
Type: single nucleotide variant
Location: chr16:83344984 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.19 · 1 PDB
Residue 253: the cadherin 2 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-his253 (accessed [today's date]).

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