Is CDC73 p.Pro350= (c.1050C>T) pathogenic?

CDC73 p.Pro350= (c.1050C>T) is classified Likely benign in CDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). Very rare (popmax 0.00113%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDC73 p.Pro350= (c.1050C>T)?

CDC73 p.Pro350= (c.1050C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDC73 p.Pro350= (c.1050C>T) in the general population?

CDC73 p.Pro350= (c.1050C>T) is very rare (popmax 0.00113%, sas) (gnomAD).

CDC73 p.Pro350=

c.1050C>T · rs1173703603 · VCV1776951

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.95	GERP -4.8, phastCons 0.002
Overall
CADD	6.388	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00113% South Asian · 1/88,116 alleles

Overall 6.98e-05% 1/1,433,262 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.Pro350=
Coding: c.1050C>T
MANE Select: NM_024529
dbSNP: rs1173703603
Type: single nucleotide variant
Location: chr1:193212084 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 350: the 'interaction with polr2a and paf1' region; the 'disordered' region

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

Similar variants

CDC73 p.Pro350Leu Uncertain significance ★★ ⚠ same residue
CDC73 p.Pro350Ser Uncertain significance ★★ ⚠ same residue
CDC73 p.Pro350Thr Uncertain significance ★ ⚠ same residue
CDC73 p.Pro350Ala Likely benign ★ 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 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-pro350 (accessed [today's date]).

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