Is CDC73 p.Arg292= (c.876A>G) pathogenic?

CDC73 p.Arg292= (c.876A>G) is classified Conflicting classifications of pathogenicity in CDC73 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-05-12). Ultra-rare (popmax 0.0174%, afr); Associated with hyperparathyroidism 2 with jaw tumors.

What condition is associated with CDC73 p.Arg292= (c.876A>G)?

CDC73 p.Arg292= (c.876A>G) is associated with hyperparathyroidism 2 with jaw tumors, parathyroid gland carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is CDC73 p.Arg292= (c.876A>G) in the general population?

CDC73 p.Arg292= (c.876A>G) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

How is Hyperparathyroidism-jaw tumor syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CDC73 p.Arg292=

c.876A>G · rs909578765 · VCV581596

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Conditions

hyperparathyroidism 2 with jaw tumors

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.81	donor gain · deltas
Pangolin	Δ0.67	gain · loss 0.36 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.1	GERP 1.6, phastCons 1
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,904 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00136% 22/1,613,284 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,762
Admixed American	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0016%	62,446
European (non-Finnish)	0.000509%	196,555

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.Arg292=
Coding: c.876A>G
MANE Select: NM_024529
dbSNP: rs909578765
Type: single nucleotide variant
Location: chr1:193150351 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 292: the 'interaction with polr2a and paf1' region; a UniProt-annotated variant site (found in a wilms tumor sample; somatic mutation); the 'disordered' region

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

Disease context

hyperparathyroidism 2 with jaw tumors — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: parathyroid gland carcinoma hereditary neoplastic syndrome

For Hyperparathyroidism-jaw tumor syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

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-p-arg292 (accessed [today's date]).

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