Is CDC73 c.237+28T>C pathogenic?

CDC73 c.237+28T>C is classified Benign in CDC73 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-07-07). Common (popmax 76.3%, sas) — too common for a highly-penetrant pathogenic allele; Associated with hyperparathyroidism 2 with jaw tumors.

What condition is associated with CDC73 c.237+28T>C?

CDC73 c.237+28T>C is associated with hyperparathyroidism 2 with jaw tumors (ClinVar).

How is Hyperparathyroidism-jaw tumor syndrome inherited?

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

CDC73 c.237+28T>C

Q: How common is CDC73 c.237+28T>C in the general population?

CDC73 c.237+28T>C is common (popmax 76.3%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs4466634 · VCV1231125

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 76.3%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

hyperparathyroidism 2 with jaw tumors

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +28	near-intronic (+28 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP -1.3, phastCons 0.003
Overall
CADD	6.619	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 76.3% South Asian · 63,601/83,352 alleles

Filtering AF 75.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 75.6%

Overall 66% 813,472/1,232,496 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	76.3%	1
Amishnot grpmax-eligible	73.2%	1
Middle Eastern	72.6%	1
Ashkenazi Jewishnot grpmax-eligible	67.5%	1
European (non-Finnish)	67.4%	1
Remaining individualsnot grpmax-eligible	66.2%	2
Admixed American	64.6%	2
Finnishnot grpmax-eligible	61.6%	2
African / African-American	52%	2
East Asian	48.1%	2

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.237+28T>C
MANE Select: NM_024529
dbSNP: rs4466634
Type: single nucleotide variant
Location: chr1:193125245 (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

For Hyperparathyroidism-jaw tumor syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

CDC73 c.131+1G>A Pathogenic/Likely pathogenic ★★ same condition
CDC73 c.513-1G>A Likely pathogenic ★★ same condition
CDC73 p.Arg139Ter Pathogenic ★★ same condition
CDC73 p.Arg222Ter Pathogenic ★★ same condition
CDC73 p.Arg268Ter Pathogenic/Likely pathogenic ★★ same condition
CDC73 p.Arg399Ter Pathogenic/Likely pathogenic ★★ same condition
CDC73 p.Arg76Ter Pathogenic ★★ same condition
CDC73 p.Arg91Ter 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-237-plus-28t-c (accessed [today's date]).

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