Is CDH22 p.Ala15Pro (c.43G>C) pathogenic?

CDH22 p.Ala15Pro (c.43G>C) is classified Uncertain significance in CDH22 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely benign (0.1179); Very rare (popmax 0.00404%, nfe).

How common is CDH22 p.Ala15Pro (c.43G>C) in the general population?

CDH22 p.Ala15Pro (c.43G>C) is very rare (popmax 0.00404%, nfe) (gnomAD).

What do computational predictors say about CDH22 p.Ala15Pro (c.43G>C)?

AlphaMissense predicts likely benign (score 0.1179) — an in-silico prediction, not a clinical call.

CDH22 p.Ala15Pro

c.43G>C · VCV3830115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1179 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00404%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1179	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -6.20	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 0.33	phastCons 0.004
Regional constraint	o/e 0.78	unconstrained · MANE · 76 kb · p 5.2e-13 · regional, not allelic
Overall
CADD	20.5	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 0.00404% European (non-Finnish) · 45/1,114,518 alleles

Filtering AF 0.00308% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00342% 45/1,317,148 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.Ala15Pro
Coding: c.43G>C
MANE Select: NM_021248
Type: single nucleotide variant
Location: chr20:46251252 (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.Ala782Val Benign ★★ ⚠ same type
CDH22 p.Pro624= Benign ★★ same type
CDH22 p.Ala121Val 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
CDH22 p.Ala450Thr Uncertain significance ★ ⚠ same type
CDH22 p.Ala46Val 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-ala15pro (accessed [today's date]).

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