Is CDH10 p.Ile584Val (c.1750A>G) pathogenic?

CDH10 p.Ile584Val (c.1750A>G) is classified Uncertain significance in CDH10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.0859); Ultra-rare (popmax 0.0253%, nfe).

How common is CDH10 p.Ile584Val (c.1750A>G) in the general population?

CDH10 p.Ile584Val (c.1750A>G) is ultra-rare (popmax 0.0253%, nfe) (gnomAD).

What do computational predictors say about CDH10 p.Ile584Val (c.1750A>G)?

AlphaMissense predicts likely benign (score 0.0859) — an in-silico prediction, not a clinical call.

CDH10 p.Ile584Val

c.1750A>G · rs753551926 · VCV3141068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0859 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0859	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -4.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 46 kb · p 1.8e-06 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0253% European (non-Finnish) · 298/1,179,922 alleles

Filtering AF 0.0229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.0193% 311/1,613,910 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0253%	3,959
Remaining individualsnot grpmax-eligible	0.0176%	5,680
African / African-American	0.00267%	37,456

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: CDH10
Protein: p.Ile584Val
Coding: c.1750A>G
MANE Select: NM_006727
dbSNP: rs753551926
Type: single nucleotide variant
Location: chr5:24491702 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 78.29
Residue 584: the cadherin 5 domain

Full CDH10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH10 p.Met316Ile Uncertain significance ★★ ⚠ same type
CDH10 p.Thr159Met Uncertain significance ★★ ⚠ same type
CDH10 p.Glu469= Benign ★★ same type
CDH10 p.Gly673= Benign ★★ same type
CDH10 p.Ala296Thr Uncertain significance ★ ⚠ same type
CDH10 p.Ala501Val Uncertain significance ★ ⚠ same type
CDH10 p.Ala530Val Uncertain significance ★ ⚠ same type
CDH10 p.Arg128Cys 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/cdh10-p-ile584val (accessed [today's date]).

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