Is CDH24 p.Arg316Pro (c.947G>C) pathogenic?

CDH24 p.Arg316Pro (c.947G>C) is classified Uncertain significance in CDH24 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: ambiguous (0.5632); Absent from gnomAD v4.1.

How common is CDH24 p.Arg316Pro (c.947G>C) in the general population?

CDH24 p.Arg316Pro (c.947G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH24 p.Arg316Pro (c.947G>C)?

AlphaMissense predicts ambiguous (score 0.5632) — an in-silico prediction, not a clinical call.

CDH24 p.Arg316Pro

c.947G>C · VCV4837047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5632 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5632	ambiguous
REVEL	0.15	moderately benign-leaning
SaProt	LLR -12.38	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.032	GERP -4.1, phastCons 0.86
Regional constraint	o/e 0.83	unconstrained · MANE · 6,685 bp · p 9e-07 · regional, not allelic
Overall
CADD	17.14	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDH24
Protein: p.Arg316Pro
Coding: c.947G>C
MANE Select: NM_144985
Type: single nucleotide variant
Location: chr14:23054166 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.54
Residue 316: the cadherin 3 domain

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

Similar variants

CDH24 p.Arg316Gln 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-arg316pro (accessed [today's date]).

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