Is CDH11 p.Arg547Ter (c.1639C>T) pathogenic?

CDH11 p.Arg547Ter (c.1639C>T) is classified Likely pathogenic in CDH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-23). Very rare (popmax 0.00169%, amr).

How common is CDH11 p.Arg547Ter (c.1639C>T) in the general population?

CDH11 p.Arg547Ter (c.1639C>T) is very rare (popmax 0.00169%, amr) (gnomAD).

CDH11 p.Arg547Ter

c.1639C>T · rs1177793851 · VCV987332

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00169%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 11 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -1.2, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% Admixed American · 1/59,106 alleles

Overall 0.000657% 1/152,188 alleles · very rare

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: CDH11
Protein: p.Arg547Ter
Coding: c.1639C>T
MANE Select: NM_001797
dbSNP: rs1177793851
Type: single nucleotide variant
Location: chr16:64971582 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 547: the cadherin 5 domain; a UniProt-annotated variant site (in esws)

Full CDH11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH11 p.Asp260Asn Pathogenic/Likely pathogenic ★★ same type
CDH11 p.Ala228Ser Uncertain significance ★★ ⚠ same type
CDH11 p.Arg556Trp Uncertain significance ★★ ⚠ same type
CDH11 p.Asp718Asn Uncertain significance ★★ ⚠ same type
CDH11 p.Gly45Arg Uncertain significance ★★ ⚠ same type
CDH11 p.Gly618Ser Uncertain significance ★★ ⚠ same type
CDH11 p.Ile649Val Uncertain significance ★★ ⚠ same type
CDH11 c.1253+43G>C 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/cdh11-p-arg547ter (accessed [today's date]).

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