Is CDH18 p.Thr413Ser (c.1238C>G) pathogenic?

CDH18 p.Thr413Ser (c.1238C>G) is classified Uncertain significance in CDH18 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-26). AlphaMissense: likely benign (0.0681); Very rare (popmax 8.48e-05%, nfe).

How common is CDH18 p.Thr413Ser (c.1238C>G) in the general population?

CDH18 p.Thr413Ser (c.1238C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CDH18 p.Thr413Ser (c.1238C>G)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

CDH18 p.Thr413Ser

c.1238C>G · rs17856908 · VCV2541306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -3.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 139 kb · p 0.64 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,874 alleles

Overall 6.84e-05% 1/1,461,692 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.Thr413Ser
Coding: c.1238C>G
MANE Select: NM_004934
dbSNP: rs17856908
Type: single nucleotide variant
Location: chr5:19571594 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.57
Residue 413: the cadherin 4 domain

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

Similar variants

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
CDH18 p.Ala618Thr 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-thr413ser (accessed [today's date]).

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