Is CDH22 p.Leu788Pro (c.2363T>C) pathogenic?

CDH22 p.Leu788Pro (c.2363T>C) is classified Uncertain significance in CDH22 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: ambiguous (0.4767); Very rare (popmax 0.00118%, sas).

How common is CDH22 p.Leu788Pro (c.2363T>C) in the general population?

CDH22 p.Leu788Pro (c.2363T>C) is very rare (popmax 0.00118%, sas) (gnomAD).

What do computational predictors say about CDH22 p.Leu788Pro (c.2363T>C)?

AlphaMissense predicts ambiguous (score 0.4767) — an in-silico prediction, not a clinical call.

CDH22 p.Leu788Pro

c.2363T>C · rs2085722215 · VCV3141200

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4767 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00118%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4767	ambiguous
REVEL	0.775	moderately pathogenic-leaning
SaProt	LLR -10.50	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 396 bp · p 0.36 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00118% South Asian · 1/84,690 alleles

Overall 7.15e-05% 1/1,397,728 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: CDH22
Protein: p.Leu788Pro
Coding: c.2363T>C
MANE Select: NM_021248
dbSNP: rs2085722215
Type: single nucleotide variant
Location: chr20:46174630 (GRCh38)
Gene constraint: LOEUF 0.782 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.19

Full CDH22 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH22 p.Leu788Met Uncertain significance ★ ⚠ same residue
CDH22 p.Ala782Val Benign ★★ ⚠ same type
CDH22 p.Pro624= Benign ★★ same type
CDH22 p.Ala121Val Uncertain significance ★ ⚠ same type
CDH22 p.Ala15Pro Uncertain significance ★ ⚠ same type
CDH22 p.Ala19Thr Uncertain significance ★ ⚠ same type
CDH22 p.Ala384Thr Uncertain significance ★ ⚠ same type
CDH22 p.Ala39Val 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/cdh22-p-leu788pro (accessed [today's date]).

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