Is CDH24 p.Arg217Gln (c.650G>A) pathogenic?

CDH24 p.Arg217Gln (c.650G>A) is classified Uncertain significance in CDH24 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely pathogenic (0.9226); Very rare (popmax 0.0022%, sas).

How common is CDH24 p.Arg217Gln (c.650G>A) in the general population?

CDH24 p.Arg217Gln (c.650G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CDH24 p.Arg217Gln (c.650G>A)?

AlphaMissense predicts likely pathogenic (score 0.9226) — an in-silico prediction, not a clinical call.

CDH24 p.Arg217Gln

c.650G>A · rs778309563 · VCV2613869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9226 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9226	likely pathogenic
REVEL	0.536	indeterminate
SaProt	LLR -15.41	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 6,685 bp · p 9e-07 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0022% South Asian · 2/91,072 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,536
Admixed American	0.00167%	59,994
European (non-Finnish)	0.000593%	168,572

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: CDH24
Protein: p.Arg217Gln
Coding: c.650G>A
MANE Select: NM_144985
dbSNP: rs778309563
Type: single nucleotide variant
Location: chr14:23054640 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.54
Residue 217: the cadherin 2 domain

Full CDH24 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH24 c.1363+390G>A Uncertain significance ★ ⚠ same type
CDH24 c.1363+418G>T Uncertain significance ★ ⚠ same type
CDH24 c.1363+470A>G Uncertain significance ★ ⚠ same type
CDH24 c.1363+476G>A Uncertain significance ★ ⚠ same type
CDH24 c.1363+476G>T Uncertain significance ★ ⚠ same type
CDH24 c.1363+486C>T Uncertain significance ★ ⚠ same type
CDH24 p.Ala119Val Uncertain significance ★ ⚠ same type
CDH24 p.Ala174Val 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/cdh24-p-arg217gln (accessed [today's date]).

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