CDC73 p.Pro33Ala
c.97C>G · VCV4223480
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4185 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense no call
Conditions
1
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4185 | ambiguous |
|---|---|---|
| REVEL | 0.735 | pathogenic-leaning |
| SaProt | LLR -12.25 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.3 | GERP 1.6, phastCons 1 |
| Regional constraint | o/e 0.57 | unconstrained · MANE · 16 kb · p 1.1e-08 · regional, not allelic |
| Overall | ||
| CADD | 24.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CDC73
- Protein
- p.Pro33Ala
- Coding
- c.97C>G
- MANE Select
- NM_024529
- Type
- single nucleotide variant
- Location
- chr1:193122297 (GRCh38)
- Gene constraint
- LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.94 · 21 PDB
- Residue 33
- a β-strand
Similar variants
- CDC73 p.Pro33Thr Uncertain significance ★★ ⚠ same residue
- CDC73 p.Pro33= Likely benign ★★ 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 p.Arg120Ter Pathogenic ★★ same condition
- CDC73 p.Arg126Ter Pathogenic/Likely pathogenic ★★ same condition
- CDC73 p.Arg139Ter 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-pro33ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown