Is CDH12 p.Gln60= (c.180A>G) pathogenic?

CDH12 p.Gln60= (c.180A>G) is classified Benign in CDH12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Rare (popmax 0.172%, nfe).

How common is CDH12 p.Gln60= (c.180A>G) in the general population?

CDH12 p.Gln60= (c.180A>G) is rare (popmax 0.172%, nfe) (gnomAD).

CDH12 p.Gln60=

c.180A>G · rs142320441 · VCV708682

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.172%, nfe)

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 -5.9	GERP -5
Overall
CADD	1.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.172% European (non-Finnish) · 2,035/1,179,874 alleles

Filtering AF 0.166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.164%

Overall 0.148% 2,393/1,613,934 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.476%	210
Remaining individualsnot grpmax-eligible	0.173%	579
European (non-Finnish)grpmax	0.172%	580
Middle Eastern	0.165%	606
Admixed American	0.0917%	1,091
African / African-American	0.0293%	3,410
Finnishnot grpmax-eligible	0.0156%	6,403
South Asian	0.0132%	7,590

Ashkenazi Jewish 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: CDH12
Protein: p.Gln60=
Coding: c.180A>G
MANE Select: NM_004061
dbSNP: rs142320441
Type: single nucleotide variant
Location: chr5:22078497 (GRCh38)
Gene constraint: LOEUF 0.668 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.19
Residue 60: the cadherin 1 domain

Full CDH12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH12 c.1003-3C>T Benign ★★ same type
CDH12 p.Asp780= Likely benign ★★ same type
CDH12 p.Glu349Asp Benign ★★ ⚠ same type
CDH12 p.Glu34Gln Benign ★★ same type
CDH12 p.Ile475Thr Benign ★★ ⚠ same type
CDH12 p.Ile598= Likely benign ★★ same type
CDH12 p.Pro213= Benign ★★ same type
CDH12 p.Thr260= 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/cdh12-p-gln60 (accessed [today's date]).

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