Is CDC73 p.Lys393= (c.1179G>A) pathogenic?

CDC73 p.Lys393= (c.1179G>A) is classified Benign/Likely benign in CDC73 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-27). Ultra-rare (popmax 0.0424%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDC73 p.Lys393= (c.1179G>A)?

CDC73 p.Lys393= (c.1179G>A) is associated with hereditary neoplastic syndrome, parathyroid gland carcinoma (ClinVar).

How common is CDC73 p.Lys393= (c.1179G>A) in the general population?

CDC73 p.Lys393= (c.1179G>A) is ultra-rare (popmax 0.0424%, eas) (gnomAD).

CDC73 p.Lys393=

c.1179G>A · rs200738107 · VCV531666

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0424%, eas)

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 6.6	GERP 0.89, phastCons 1
Overall
CADD	9.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0424% East Asian · 19/44,852 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00136% 22/1,613,700 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0424%	2,361
Remaining individualsnot grpmax-eligible	0.0016%	62,496
South Asian	0.0011%	91,076
European (non-Finnish)	8.48e-05%	1,179,746

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.Lys393=
Coding: c.1179G>A
MANE Select: NM_024529
dbSNP: rs200738107
Type: single nucleotide variant
Location: chr1:193233017 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 393: the 'interaction with polr2a and paf1' region; an α-helix

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.Lys393Ter Pathogenic ★ same residue
CDC73 p.Lys393Gln 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
CDC73 c.513-1G>A Likely 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-lys393 (accessed [today's date]).

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