Is CDH24 p.Ser267Cys (c.800C>G) pathogenic?

CDH24 p.Ser267Cys (c.800C>G) is classified Uncertain significance in CDH24 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-05). AlphaMissense: ambiguous (0.4589); Very rare (popmax 0.00224%, eas).

How common is CDH24 p.Ser267Cys (c.800C>G) in the general population?

CDH24 p.Ser267Cys (c.800C>G) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about CDH24 p.Ser267Cys (c.800C>G)?

AlphaMissense predicts ambiguous (score 0.4589) — an in-silico prediction, not a clinical call.

CDH24 p.Ser267Cys

c.800C>G · rs61976366 · VCV2593597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Computational evidence

Protein change
AlphaMissense	0.4589	ambiguous
REVEL	0.323	indeterminate
SaProt	LLR -12.28	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 6,685 bp · p 9e-07 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,728 alleles

Overall 6.88e-05% 1/1,452,762 alleles · very rare

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.Ser267Cys
Coding: c.800C>G
MANE Select: NM_144985
dbSNP: rs61976366
Type: single nucleotide variant
Location: chr14:23054313 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.54
Residue 267: the cadherin 3 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-ser267cys (accessed [today's date]).

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