Is CDH18 p.Ser647= (c.1941A>C) pathogenic?

CDH18 p.Ser647= (c.1941A>C) is classified Likely benign in CDH18 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-08-29). Very rare (popmax 0.000932%, nfe); Associated with CDH18-related disorder.

What condition is associated with CDH18 p.Ser647= (c.1941A>C)?

CDH18 p.Ser647= (c.1941A>C) is associated with CDH18-related disorder (ClinVar).

How common is CDH18 p.Ser647= (c.1941A>C) in the general population?

CDH18 p.Ser647= (c.1941A>C) is very rare (popmax 0.000932%, nfe) (gnomAD).

CDH18 p.Ser647=

c.1941A>C · rs751281107 · VCV3044783

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Conditions

CDH18-related disorder

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 -8.6	GERP -5.8
Overall
CADD	0.618	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,808 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000753% 11/1,461,528 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: CDH18
Protein: p.Ser647=
Coding: c.1941A>C
MANE Select: NM_004934
dbSNP: rs751281107
Type: single nucleotide variant
Location: chr5:19473658 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.57

Full CDH18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CDH18-related disorder

Similar variants

CDH18 p.Thr473Pro Likely benign same condition
CDH18 p.Pro386= Benign ★★ same type
CDH18 p.Ser194= Benign ★★ same type
CDH18 p.Ala435Thr Uncertain significance ★ ⚠ same type
CDH18 p.Ala518Asp Uncertain significance ★ ⚠ same type
CDH18 p.Ala602Thr Uncertain significance ★ ⚠ same type
CDH18 p.Ala609Pro Uncertain significance ★ ⚠ same type
CDH18 p.Ala615Gly Uncertain significance ★ ⚠ 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/cdh18-p-ser647 (accessed [today's date]).

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