Is CDC73 p.Lys392= (c.1176G>A) pathogenic?

CDC73 p.Lys392= (c.1176G>A) is classified Likely benign in CDC73 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-11). Very rare (popmax 0.00988%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDC73 p.Lys392= (c.1176G>A)?

CDC73 p.Lys392= (c.1176G>A) is associated with hereditary neoplastic syndrome, parathyroid gland carcinoma (ClinVar).

How common is CDC73 p.Lys392= (c.1176G>A) in the general population?

CDC73 p.Lys392= (c.1176G>A) is very rare (popmax 0.00988%, sas) (gnomAD).

CDC73 p.Lys392=

c.1176G>A · rs767993995 · VCV1541073

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor loss, 21 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.1	GERP 0.88, phastCons 1
Overall
CADD	3.945	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00988% South Asian · 9/91,072 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.000558% 9/1,613,656 alleles · very rare exomes 8/1,461,572 · genomes 1/152,084 · joint denominator

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.Lys392=
Coding: c.1176G>A
MANE Select: NM_024529
dbSNP: rs767993995
Type: single nucleotide variant
Location: chr1:193233014 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 392: 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.Lys392Asn Uncertain significance ★ ⚠ same residue
CDC73 p.Lys392fs Pathogenic ★ 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-lys392 (accessed [today's date]).

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