Is CDC73 p.Lys393Ter (c.1177A>T) pathogenic?

CDC73 p.Lys393Ter (c.1177A>T) is classified Pathogenic in CDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). Absent from gnomAD v4.1; Associated with parathyroid gland carcinoma.

What condition is associated with CDC73 p.Lys393Ter (c.1177A>T)?

CDC73 p.Lys393Ter (c.1177A>T) is associated with parathyroid gland carcinoma (ClinVar).

How common is CDC73 p.Lys393Ter (c.1177A>T) in the general population?

CDC73 p.Lys393Ter (c.1177A>T) is absent from gnomAD v4.1 (gnomAD).

How is Parathyroid carcinoma inherited?

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

CDC73 p.Lys393Ter

c.1177A>T · VCV4730979

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

parathyroid gland carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 14 of 17
Splicing
SpliceAI	Δ0.54	acceptor loss, 22 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDC73
Protein: p.Lys393Ter
Coding: c.1177A>T
MANE Select: NM_024529
Type: single nucleotide variant
Location: chr1:193233015 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 393: 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.Lys393= Benign/Likely benign ★★ same residue
CDC73 p.Lys393Gln Uncertain significance ★ ⚠ same residue
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

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-lys393ter (accessed [today's date]).

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