Is CDH24 p.Asp471His (c.1411G>C) pathogenic?

CDH24 p.Asp471His (c.1411G>C) is classified Uncertain significance in CDH24 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). AlphaMissense: likely pathogenic (0.9625); Very rare (popmax 0.000678%, nfe).

How common is CDH24 p.Asp471His (c.1411G>C) in the general population?

CDH24 p.Asp471His (c.1411G>C) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CDH24 p.Asp471His (c.1411G>C)?

AlphaMissense predicts likely pathogenic (score 0.9625) — an in-silico prediction, not a clinical call.

CDH24 p.Asp471His

c.1411G>C · rs756508966 · VCV3141230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9625 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9625	likely pathogenic
REVEL	0.779	moderately pathogenic-leaning
SaProt	LLR -14.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 6,685 bp · p 9e-07 · regional, not allelic
Overall
CADD	31.0	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 D509H vs ClinVar D471H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,022 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,613,912 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)grpmax	0.000678%	147,503

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp471His
Coding: c.1411G>C
MANE Select: NM_144985
dbSNP: rs756508966
Type: single nucleotide variant
Location: chr14:23049896 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.54
Residue 471: the cadherin 4 domain

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

Similar variants

CDH24 p.Asp471Asn 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
CDH24 p.Ala119Val 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-asp471his (accessed [today's date]).

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