Is CDC73 p.Val230Ala (c.689T>C) pathogenic?

CDC73 p.Val230Ala (c.689T>C) is classified Uncertain significance in CDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-06). AlphaMissense: likely pathogenic (0.7708); Absent from gnomAD v4.1; Associated with parathyroid gland carcinoma.

What condition is associated with CDC73 p.Val230Ala (c.689T>C)?

CDC73 p.Val230Ala (c.689T>C) is associated with parathyroid gland carcinoma (ClinVar).

How common is CDC73 p.Val230Ala (c.689T>C) in the general population?

CDC73 p.Val230Ala (c.689T>C) is absent from gnomAD v4.1 (gnomAD).

How is Parathyroid carcinoma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CDC73 p.Val230Ala (c.689T>C)?

AlphaMissense predicts likely pathogenic (score 0.7708) — an in-silico prediction, not a clinical call.

CDC73 p.Val230Ala

c.689T>C · rs1558285020 · VCV654339

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7708 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

parathyroid gland carcinoma

Computational evidence

Protein change
AlphaMissense	0.7708	likely pathogenic
REVEL	0.369	indeterminate
SaProt	LLR -8.56	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 109 kb · p 8.5e-19 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Val230Ala
Coding: c.689T>C
MANE Select: NM_024529
dbSNP: rs1558285020
Type: single nucleotide variant
Location: chr1:193142026 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 230: the 'interaction with polr2a and paf1' region; the 'interaction with ctnnb1' region

Full CDC73 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

parathyroid gland carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Parathyroid carcinoma (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

CDC73 p.Val230Ile Uncertain significance ★★ ⚠ same residue
CDC73 p.Val230= Likely benign ★★ same residue
CDC73 p.Val230Glu Uncertain significance ★ ⚠ same residue
CDC73 p.Val230fs 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

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-val230ala (accessed [today's date]).

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