Is CDC73 p.Ser111= (c.333C>T) pathogenic?

CDC73 p.Ser111= (c.333C>T) is classified Likely benign in CDC73 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-17). Ultra-rare (popmax 0.0165%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with CDC73 p.Ser111= (c.333C>T)?

CDC73 p.Ser111= (c.333C>T) is associated with hereditary neoplastic syndrome, hyperparathyroidism 1, hyperparathyroidism 2 with jaw tumors (ClinVar).

How common is CDC73 p.Ser111= (c.333C>T) in the general population?

CDC73 p.Ser111= (c.333C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CDC73 p.Ser111=

c.333C>T · rs374834265 · VCV412634

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -0.16	GERP -2.2, phastCons 0.72
Overall
CADD	10.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.00906% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00845%

Overall 0.00868% 140/1,613,536 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
African / African-American	0.0133%	7,499
European (non-Finnish)	0.0106%	9,437
Remaining individualsnot grpmax-eligible	0.0032%	31,243
East Asian	0.00223%	44,824
South Asian	0.0011%	91,066

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.Ser111=
Coding: c.333C>T
MANE Select: NM_024529
dbSNP: rs374834265
Type: single nucleotide variant
Location: chr1:193135416 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB

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: hyperparathyroidism 1 hyperparathyroidism 2 with jaw tumors parathyroid gland carcinoma

Similar variants

CDC73 p.Ser111Gly Uncertain significance ★ ⚠ same residue
CDC73 p.Ser111fs 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-ser111 (accessed [today's date]).

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