Is CDH7 p.Thr159= (c.477G>A) pathogenic?

CDH7 p.Thr159= (c.477G>A) is classified Benign in CDH7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-09). Common (popmax 10.4%, amr) — too common for a highly-penetrant pathogenic allele.

CDH7 p.Thr159=

Q: How common is CDH7 p.Thr159= (c.477G>A) in the general population?

CDH7 p.Thr159= (c.477G>A) is common (popmax 10.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.477G>A · rs17075229 · VCV1244452

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 10.4%, amr) — 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 -9.8	GERP -4.9
Overall
CADD	0.089	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.4% Admixed American · 6,237/59,952 alleles

Filtering AF 10.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.1%

Overall 2% 32,236/1,611,472 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	10.4%	10
Finnishnot grpmax-eligible	3.15%	32
European (non-Finnish)	1.82%	55
Remaining individualsnot grpmax-eligible	1.62%	62
South Asian	1.07%	93
Amishnot grpmax-eligible	0.987%	101
Ashkenazi Jewishnot grpmax-eligible	0.879%	114
African / African-American	0.388%	258
Middle Eastern	0.364%	275
East Asian	0.0179%	5,598

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: CDH7
Protein: p.Thr159=
Coding: c.477G>A
MANE Select: NM_021153 · reported on NM_004361
dbSNP: rs17075229
Type: single nucleotide variant
Location: chr18:65809970 (GRCh38)
Structure: AlphaFold pLDDT 78.14
Residue 159: the cadherin 2 domain

Full CDH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH7 p.Thr159Ala Uncertain significance ★ ⚠ same residue
CDH7 p.Thr159Met Uncertain significance ★ ⚠ same residue
CDH19 p.Pro558= Benign ★★ same type
CDH19 p.Thr89Ile Benign ★★ same type
CDH7 c.1612+22C>T Benign ★★ same type
CDH7 c.1612+24A>T Benign ★★ same type
CDH7 c.1612+81T>C Benign ★★ same type
CDH7 c.1864+225A>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/cdh7-p-thr159 (accessed [today's date]).

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