Is CDC73 p.Leu173= (c.519G>A) pathogenic?

CDC73 p.Leu173= (c.519G>A) is classified Likely benign in CDC73 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-26). Very rare (popmax 0.00153%, nfe); Associated with hyperparathyroidism 2 with jaw tumors.

What condition is associated with CDC73 p.Leu173= (c.519G>A)?

CDC73 p.Leu173= (c.519G>A) is associated with hyperparathyroidism 2 with jaw tumors, hyperparathyroidism 1, parathyroid gland carcinoma (ClinVar).

How common is CDC73 p.Leu173= (c.519G>A) in the general population?

CDC73 p.Leu173= (c.519G>A) is very rare (popmax 0.00153%, nfe) (gnomAD).

How is Hyperparathyroidism-jaw tumor syndrome inherited?

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

CDC73 p.Leu173=

c.519G>A · rs749039338 · VCV1150036

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Conditions

hyperparathyroidism 2 with jaw tumors

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 2.9	GERP 1.1, phastCons 1
Overall
CADD	6.764	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00153% European (non-Finnish) · 18/1,177,778 alleles

Filtering AF 0.000955% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000788%

Overall 0.0013% 21/1,611,184 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,186
European (non-Finnish)grpmax	0.00153%	65,432
African / African-American	0.00134%	74,856

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu173=
Coding: c.519G>A
MANE Select: NM_024529
dbSNP: rs749039338
Type: single nucleotide variant
Location: chr1:193141856 (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

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

Also linked: hyperparathyroidism 1 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-leu173 (accessed [today's date]).

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