Is CDC73 p.Glu400= (c.1200A>G) pathogenic?

CDC73 p.Glu400= (c.1200A>G) is classified Likely benign in CDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-02). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDC73 p.Glu400= (c.1200A>G)?

CDC73 p.Glu400= (c.1200A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDC73 p.Glu400= (c.1200A>G) in the general population?

CDC73 p.Glu400= (c.1200A>G) is absent from gnomAD v4.1 (gnomAD).

CDC73 p.Glu400=

c.1200A>G · VCV3998681

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 4.2	GERP -0.88, phastCons 1
Overall
CADD	8.178	PHRED · no single calibrated threshold — expert panels disagree

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.Glu400=
Coding: c.1200A>G
MANE Select: NM_024529
Type: single nucleotide variant
Location: chr1:193233038 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 400: the 'interaction with polr2a and paf1' 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.Glu400fs Pathogenic ★ same residue
CDC73 p.Glu400Asp 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 p.Arg120Ter Pathogenic ★★ same condition
CDC73 p.Arg126Ter Pathogenic/Likely pathogenic ★★ same condition
CDC73 p.Arg139Ter 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-glu400 (accessed [today's date]).

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