Is CDH24 p.Ala398Val (c.1193C>T) pathogenic?

CDH24 p.Ala398Val (c.1193C>T) is classified Uncertain significance in CDH24 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-03). AlphaMissense: likely pathogenic (0.7733); Very rare (popmax 0.00451%, eas).

How common is CDH24 p.Ala398Val (c.1193C>T) in the general population?

CDH24 p.Ala398Val (c.1193C>T) is very rare (popmax 0.00451%, eas) (gnomAD).

What do computational predictors say about CDH24 p.Ala398Val (c.1193C>T)?

AlphaMissense predicts likely pathogenic (score 0.7733) — an in-silico prediction, not a clinical call.

CDH24 p.Ala398Val

c.1193C>T · VCV3265284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7733 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00451%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7733	likely pathogenic
REVEL	0.595	indeterminate
SaProt	LLR -12.31	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 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 6,685 bp · p 9e-07 · regional, not allelic
Overall
CADD	28.5	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 0.00451% East Asian · 2/44,358 alleles

Filtering AF 0.00167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00144%

Overall 0.00238% 38/1,593,934 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00451%	22,179
South Asian	0.00443%	22,563
Remaining individualsnot grpmax-eligible	0.00325%	30,743
African / African-American	0.00268%	37,310
European (non-Finnish)	0.0024%	41,590

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.Ala398Val
Coding: c.1193C>T
MANE Select: NM_144985
Type: single nucleotide variant
Location: chr14:23053529 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.54
Residue 398: the cadherin 4 domain

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

Similar variants

CDH24 p.Ala398Glu Uncertain significance ★ ⚠ same residue
CDH24 p.Ala398Thr Uncertain significance ★ ⚠ same residue
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

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-ala398val (accessed [today's date]).

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