Is CDC73 p.Arg513= (c.1539G>A) pathogenic?

CDC73 p.Arg513= (c.1539G>A) is classified Likely benign in CDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-29). Very rare (popmax 0.0011%, sas); Associated with parathyroid gland carcinoma.

What condition is associated with CDC73 p.Arg513= (c.1539G>A)?

CDC73 p.Arg513= (c.1539G>A) is associated with parathyroid gland carcinoma (ClinVar).

How common is CDC73 p.Arg513= (c.1539G>A) in the general population?

CDC73 p.Arg513= (c.1539G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Parathyroid carcinoma inherited?

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

CDC73 p.Arg513=

c.1539G>A · VCV4726722

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 0.66	GERP -3.4, phastCons 1
Overall
CADD	5.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,054 alleles

Overall 0.000137% 2/1,460,538 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,054
European (non-Finnish)	8.48e-05%	1,178,832

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.Arg513=
Coding: c.1539G>A
MANE Select: NM_024529
Type: single nucleotide variant
Location: chr1:193249851 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 513: the 'interaction with polr2a and paf1' region; an α-helix

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

For Parathyroid carcinoma (Orphanet):

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

Similar variants

CDC73 p.Arg513Gln Uncertain significance ★★ ⚠ same residue
CDC73 p.Arg513Trp 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-arg513 (accessed [today's date]).

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