CDC73 p.Val447=
c.1341G>A · rs771409544 · VCV1138938
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
hereditary neoplastic syndrome
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 0.16 | GERP -3.5, phastCons 0.82 |
| Overall | ||
| CADD | 5.912 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,020 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000205%
3/1,461,552 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,020 |
| European (non-Finnish) | 0.00017% | 589,873 |
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
- CDC73
- Protein
- p.Val447=
- Coding
- c.1341G>A
- MANE Select
- NM_024529
- dbSNP
- rs771409544
- Type
- single nucleotide variant
- Location
- chr1:193236280 (GRCh38)
- Gene constraint
- LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.94 · 21 PDB
- Residue 447
- the 'interaction with polr2a and paf1' region
Similar variants
- CDC73 p.Val447Met Uncertain significance ★★ ⚠ same residue
- CDC73 p.Val447Leu Uncertain significance ★ ⚠ same residue
- CDC73 c.1030+2T>C Likely pathogenic ★★ same condition
- CDC73 c.131+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CDC73 c.237+1G>A Pathogenic ★★ same condition
- CDC73 c.423+1G>A Pathogenic ★★ same condition
- CDC73 c.513-1G>A Likely pathogenic ★★ same condition
- CDC73 p.Arg120Ter 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/cdc73-p-val447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown