CDC73 p.Ala2=
c.6G>A · rs1477227787 · VCV1756611
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Conditions
1
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 11 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 15.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,926 alleles
Overall
0.000657%
1/152,238 alleles · very rare
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.Ala2=
- Coding
- c.6G>A
- MANE Select
- NM_024529
- dbSNP
- rs1477227787
- Type
- single nucleotide variant
- Location
- chr1:193122206 (GRCh38)
- Gene constraint
- LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.94 · 21 PDB
- Residue 2
- a UniProt-annotated variant site (found in parathyroid adenoma samples; somatic mutation; parathyroid adenoma samples are from a patient with isolated hyperparathyroidism who also carries germline mutation p-91); a modified residue (n-acetylalanine)
Similar variants
- 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
- CDC73 p.Arg222Ter Pathogenic ★★ same condition
- CDC73 p.Arg229Ter 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-ala2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown