Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 6.55%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.5 | GERP -4.2 |
| Overall | ||
| CADD | 3.895 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.55%
African / African-American · 4,915/75,028 alleles
Filtering AF
6.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.34%
Overall
0.364%
5,873/1,614,118 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.55% | 15 |
| Admixed American | 0.61% | 164 |
| Remaining individualsnot grpmax-eligible | 0.448% | 223 |
| Middle Eastern | 0.412% | 242 |
| East Asian | 0.0334% | 2,991 |
| European (non-Finnish) | 0.0221% | 4,521 |
| South Asian | 0.011% | 9,109 |
| Finnishnot grpmax-eligible | 0.00156% | 63,990 |
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
- CDH4
- Protein
- p.Ile691=
- Coding
- c.2073C>T
- MANE Select
- NM_001794
- dbSNP
- rs6061902
- Type
- single nucleotide variant
- Location
- chr20:61929676 (GRCh38)
- Gene constraint
- LOEUF 0.533 · pLI 0.54 (gnomAD)
- Structure
- AlphaFold pLDDT 79.02
- Residue 691
- the cadherin 5 domain
Similar variants
- CDH4 p.Thr396Met Uncertain significance ★★ ⚠ same type
- CDH4 p.Val580Ile Uncertain significance ★★ ⚠ same type
- CDH4 c.1629-8C>T Benign ★★ same type
- CDH4 c.2240-4A>G Benign ★★ same type
- CDH4 p.Ala33Thr Benign ★★ same type
- CDH4 p.Ala344= Benign/Likely benign ★★ same type
- CDH4 p.Asn283= Benign/Likely benign ★★ same type
- CDH4 p.Asn450= Benign/Likely 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/cdh4-p-ile691 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown