Is CDC73 p.Ile469fs (c.1405dup) pathogenic?

CDC73 p.Ile469fs (c.1405dup) is classified Pathogenic in CDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-02). Absent from gnomAD; Associated with parathyroid gland carcinoma.

What condition is associated with CDC73 p.Ile469fs (c.1405dup)?

CDC73 p.Ile469fs (c.1405dup) is associated with parathyroid gland carcinoma (ClinVar).

How common is CDC73 p.Ile469fs (c.1405dup) in the general population?

CDC73 p.Ile469fs (c.1405dup) is absent from gnomAD (gnomAD).

How is Parathyroid carcinoma inherited?

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

CDC73 p.Ile469fs

c.1405dup · rs1677757559 · VCV938616

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 15 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.62	GERP 0.27, phastCons 0.99

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDC73
Protein: p.Ile469fs
Coding: c.1405dup
MANE Select: NM_024529
dbSNP: rs1677757559
Type: Duplication
Location: chr1:193236343 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 469: 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.Ile469Thr Uncertain significance ★★ ⚠ same residue
CDC73 p.Ile469Val 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

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-ile469fs (accessed [today's date]).

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