CUL7 p.His563=
c.1689T>C · rs753550369 · VCV911540
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00432%, nfe)
Conditions
1
3M syndrome 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7 | GERP -3.4 |
| Overall | ||
| CADD | 1.229 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00432%
European (non-Finnish) · 51/1,180,050 alleles
Filtering AF
0.00334%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00302%
Overall
0.00335%
54/1,614,090 alleles · very rare
exomes 51/1,461,894 · genomes 3/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00432% | 23,138 |
| Admixed American | 0.00167% | 60,004 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
| African / African-American | 0.00133% | 74,916 |
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
- CUL7
- Protein
- p.His563=
- Coding
- c.1689T>C
- MANE Select
- NM_014780
- dbSNP
- rs753550369
- Type
- single nucleotide variant
- Location
- chr6:43049543 (GRCh38)
- Gene constraint
- LOEUF 0.62 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.11 · 2 PDB
- Residue 563
- a turn
Similar variants
- CUL7 c.2397+1G>A Likely pathogenic ★★ same condition
- CUL7 c.2660+1G>C Pathogenic ★★ same condition
- CUL7 c.3356-2A>C Likely pathogenic ★★ same condition
- CUL7 p.Arg1440Ter Pathogenic/Likely pathogenic ★★ same condition
- CUL7 p.Arg1445Ter Pathogenic ★★ same condition
- CUL7 p.Arg1573Ter Pathogenic ★★ same condition
- CUL7 p.Arg382Ter Pathogenic ★★ same condition
- CUL7 p.Arg550Ter Pathogenic/Likely pathogenic ★★ same condition
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/cul7-p-his563 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown