Is CDC73 p.Arg171fs (c.510del) pathogenic?

CDC73 p.Arg171fs (c.510del) is classified Pathogenic in CDC73 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). Very rare (popmax 6.91e-05%); Associated with hereditary neoplastic syndrome.

What condition is associated with CDC73 p.Arg171fs (c.510del)?

CDC73 p.Arg171fs (c.510del) is associated with hereditary neoplastic syndrome, parathyroid gland carcinoma (ClinVar).

How common is CDC73 p.Arg171fs (c.510del) in the general population?

CDC73 p.Arg171fs (c.510del) is very rare (popmax 6.91e-05%) (gnomAD).

CDC73 p.Arg171fs

c.510del · rs2103123828 · VCV1459830

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.91e-05%)

Conditions

hereditary neoplastic syndrome

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 6 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.91e-05%

Overall 6.91e-05% 1/1,447,754 alleles · very rare

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
Protein: p.Arg171fs
Coding: c.510del
MANE Select: NM_024529
dbSNP: rs2103123828
Type: Deletion
Location: chr1:193138170 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: parathyroid gland carcinoma

Similar variants

CDC73 p.Asn82fs Pathogenic ★★ same condition
CDC73 p.Glu81fs Pathogenic ★★ same condition
CDC73 p.Lys209fs Pathogenic ★★ same condition
CDC73 p.Ser174fs Pathogenic ★★ same condition
CDC73 p.His528_Leu529insTer Uncertain significance ★★ same condition
CDC73 c.1031-12del Benign/Likely benign ★★ same condition
CDC73 c.1067-4del Likely benign ★★ same condition
CDC73 c.1560-11del Likely benign ★★ 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-arg171fs (accessed [today's date]).

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