Is CDC73 p.Trp43Cys (c.129G>T) pathogenic?

CDC73 p.Trp43Cys (c.129G>T) is classified Uncertain significance in CDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely pathogenic (0.995); Absent from gnomAD v4.1; Associated with hyperparathyroidism 2 with jaw tumors.

What condition is associated with CDC73 p.Trp43Cys (c.129G>T)?

CDC73 p.Trp43Cys (c.129G>T) is associated with hyperparathyroidism 2 with jaw tumors, hyperparathyroidism 1, parathyroid gland carcinoma (ClinVar).

How common is CDC73 p.Trp43Cys (c.129G>T) in the general population?

CDC73 p.Trp43Cys (c.129G>T) is absent from gnomAD v4.1 (gnomAD).

How is Hyperparathyroidism-jaw tumor syndrome inherited?

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

What do computational predictors say about CDC73 p.Trp43Cys (c.129G>T)?

AlphaMissense predicts likely pathogenic (score 0.995) — an in-silico prediction, not a clinical call.

CDC73 p.Trp43Cys

c.129G>T · VCV3574804

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hyperparathyroidism 2 with jaw tumors

Computational evidence

Protein change
AlphaMissense	0.995	likely pathogenic
REVEL	0.829	moderately pathogenic-leaning
SaProt	LLR -14.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 16 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Trp43Cys
Coding: c.129G>T
MANE Select: NM_024529
Type: single nucleotide variant
Location: chr1:193122329 (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

For Hyperparathyroidism-jaw tumor syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

CDC73 p.Trp43Ter Pathogenic ★★ same residue
CDC73 p.Trp43fs Likely pathogenic ★ same residue
CDC73 p.Trp43Arg Uncertain significance ★ ⚠ same residue
CDC73 p.Trp43Leu 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

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-trp43cys (accessed [today's date]).

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