Is CDC73 p.Tyr74fs (c.220dup) pathogenic?

CDC73 p.Tyr74fs (c.220dup) is classified Pathogenic in CDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). Ultra-rare (gnomAD MAF 1.462e-06); Associated with parathyroid gland carcinoma.

What condition is associated with CDC73 p.Tyr74fs (c.220dup)?

CDC73 p.Tyr74fs (c.220dup) is associated with parathyroid gland carcinoma (ClinVar).

How common is CDC73 p.Tyr74fs (c.220dup) in the general population?

CDC73 p.Tyr74fs (c.220dup) is ultra-rare (gnomAD MAF 1.462e-06) (gnomAD).

How is Parathyroid carcinoma inherited?

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

CDC73 p.Tyr74fs

c.220dup · rs1572142597 · VCV801586

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 1.462e-06)

Conditions

parathyroid gland carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

Global frequency 0.000146% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: CDC73
Protein: p.Tyr74fs
Coding: c.220dup
MANE Select: NM_024529
dbSNP: rs1572142597
Type: Duplication
Location: chr1:193125197 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 74: 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.Tyr74Cys Uncertain significance ★★ ⚠ same residue
CDC73 c.1367_1417+426dup Uncertain significance ★★ same condition
CDC73 c.1560-4dup Benign/Likely benign ★★ same condition
CDC73 c.829-5dup Benign/Likely benign ★★ same condition
CDC73 c.908-6dup Benign/Likely benign ★★ same condition
CDC73 p.Ala79fs Pathogenic ★ same condition
CDC73 p.Arg342fs Pathogenic ★ same condition
CDC73 p.Gln413fs 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-tyr74fs (accessed [today's date]).

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