Is CDH22 p.Pro624= (c.1872C>T) pathogenic?

CDH22 p.Pro624= (c.1872C>T) is classified Benign in CDH22 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-20). Common (popmax 6.23%, eas) — too common for a highly-penetrant pathogenic allele.

CDH22 p.Pro624=

Q: How common is CDH22 p.Pro624= (c.1872C>T) in the general population?

CDH22 p.Pro624= (c.1872C>T) is common (popmax 6.23%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1872C>T · rs73598378 · VCV773919

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.23%, eas) — too common for a highly-penetrant pathogenic allele

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 -9.4	GERP -5
Overall
CADD	2.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.23% East Asian · 2,794/44,868 alleles

Filtering AF 6.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.96%

Overall 0.299% 4,830/1,614,046 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	6.23%	16
Admixed American	2.54%	39
Remaining individualsnot grpmax-eligible	0.482%	208
South Asian	0.147%	680
Middle Eastern	0.0825%	1,212
African / African-American	0.0386%	2,588
European (non-Finnish)	0.00364%	27,442

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.Pro624=
Coding: c.1872C>T
MANE Select: NM_021248
dbSNP: rs73598378
Type: single nucleotide variant
Location: chr20:46177989 (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.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
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-pro624 (accessed [today's date]).

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