Is CDH24 p.Asp723Ala (c.2168A>C) pathogenic?

CDH24 p.Asp723Ala (c.2168A>C) is classified Uncertain significance in CDH24 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-25). AlphaMissense: likely pathogenic (0.5887); Ultra-rare (popmax 0.0268%, mid).

How common is CDH24 p.Asp723Ala (c.2168A>C) in the general population?

CDH24 p.Asp723Ala (c.2168A>C) is ultra-rare (popmax 0.0268%, mid) (gnomAD).

What do computational predictors say about CDH24 p.Asp723Ala (c.2168A>C)?

AlphaMissense predicts likely pathogenic (score 0.5887) — an in-silico prediction, not a clinical call.

CDH24 p.Asp723Ala

c.2168A>C · VCV3998988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5887 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0268%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5887	likely pathogenic
REVEL	0.893	moderately pathogenic-leaning
SaProt	LLR -11.56	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,064 bp · p 0.3 · regional, not allelic
Overall
CADD	27.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D761A vs ClinVar D723A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0268% Middle Eastern · 1/3,734 alleles

Filtering AF 0.00271% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00145%

Overall 0.000292% 4/1,371,134 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0268%	3,734
Admixed American	0.0102%	9,761

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.Asp723Ala
Coding: c.2168A>C
MANE Select: NM_144985
Type: single nucleotide variant
Location: chr14:23048158 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.54

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-asp723ala (accessed [today's date]).

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