Is CDH7 p.Val490Ile (c.1468G>A) pathogenic?

CDH7 p.Val490Ile (c.1468G>A) is classified Uncertain significance in CDH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). AlphaMissense: likely benign (0.0717); Very rare (popmax 0.00446%, eas).

How common is CDH7 p.Val490Ile (c.1468G>A) in the general population?

CDH7 p.Val490Ile (c.1468G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CDH7 p.Val490Ile (c.1468G>A)?

AlphaMissense predicts likely benign (score 0.0717) — an in-silico prediction, not a clinical call.

CDH7 p.Val490Ile

c.1468G>A · VCV3999068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0717 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0717	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -3.87	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 9.8	GERP 0.67, phastCons 1
Overall
CADD	22.3	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 0.00446% East Asian · 2/44,854 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00378% 61/1,613,382 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,427
European (non-Finnish)	0.00441%	22,684
Admixed American	0.00333%	29,987
South Asian	0.00329%	30,354
Remaining individualsnot grpmax-eligible	0.0016%	62,456
African / African-American	0.00134%	74,866

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: CDH7
Protein: p.Val490Ile
Coding: c.1468G>A
MANE Select: NM_021153 · reported on NM_004361
Type: single nucleotide variant
Location: chr18:65859020 (GRCh38)
Structure: AlphaFold pLDDT 78.14
Residue 490: the cadherin 5 domain

Full CDH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH19 p.Pro558= Benign ★★ same type
CDH19 p.Thr89Ile Benign ★★ same type
CDH7 c.1612+22C>T Benign ★★ same type
CDH7 c.1612+24A>T Benign ★★ same type
CDH7 c.1612+81T>C Benign ★★ same type
CDH7 c.1864+225A>G Benign ★★ same type
CDH7 c.210+52G>A Benign ★★ same type
CDH7 c.210+56T>G Benign ★★ 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/cdh7-p-val490ile (accessed [today's date]).

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