Is CDC73 p.Val387= (c.1161C>G) pathogenic?

CDC73 p.Val387= (c.1161C>G) is classified Likely benign in CDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-30). Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with CDC73 p.Val387= (c.1161C>G)?

CDC73 p.Val387= (c.1161C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDC73 p.Val387= (c.1161C>G) in the general population?

CDC73 p.Val387= (c.1161C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

CDC73 p.Val387=

c.1161C>G · rs1572215263 · VCV1736814

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 -2.7	GERP -3.5
Overall
CADD	2.698	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,962 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,460,848 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,962
European (non-Finnish)	0.00017%	589,570

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.Val387=
Coding: c.1161C>G
MANE Select: NM_024529
dbSNP: rs1572215263
Type: single nucleotide variant
Location: chr1:193232999 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 387: 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.Val387Ile 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
CDC73 p.Arg222Ter 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-val387 (accessed [today's date]).

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