Is CDC73 c.*12C>A pathogenic?

CDC73 c.12C>A is classified Benign/Likely benign in CDC73 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-01). Rare (popmax 0.31%, nfe); Associated with parathyroid gland carcinoma.

What condition is associated with CDC73 c.*12C>A?

CDC73 c.*12C>A is associated with parathyroid gland carcinoma, hyperparathyroidism 1, hyperparathyroidism 2 with jaw tumors (ClinVar).

How common is CDC73 c.*12C>A in the general population?

CDC73 c.*12C>A is rare (popmax 0.31%, nfe) (gnomAD).

How is Parathyroid carcinoma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

CDC73 c.*12C>A

rs193025205 · VCV221109

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.31%, nfe)

Conditions

parathyroid gland carcinoma

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 -0.016	GERP -0.99
Non-coding constraint	Z 0.62	1 kb window · o/e 0.95 · regional · uncalibrated
Overall
CADD	4.633	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.31% European (non-Finnish) · 3,641/1,172,726 alleles

Filtering AF 0.302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.299%

Overall 0.249% 3,994/1,605,314 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.31%	322
Finnishnot grpmax-eligible	0.28%	357
Remaining individualsnot grpmax-eligible	0.196%	510
African / African-American	0.0414%	2,413
Ashkenazi Jewishnot grpmax-eligible	0.0339%	2,949
Admixed American	0.0184%	5,431

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
Coding: c.*12C>A
MANE Select: NM_024529
dbSNP: rs193025205
Type: single nucleotide variant
Location: chr1:193250724 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB

Full CDC73 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

parathyroid gland carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hyperparathyroidism 1 hyperparathyroidism 2 with jaw tumors

For Parathyroid carcinoma (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: <1 / 1 000 000 (Europe)

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 c.423+1G>A Pathogenic ★★ same condition
CDC73 c.513-1G>A Likely 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-c-star-12c-a (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown