Is CDC73 p.Gln14Arg (c.41A>G) pathogenic?

CDC73 p.Gln14Arg (c.41A>G) is classified Uncertain significance in CDC73 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-24). AlphaMissense: ambiguous (0.4021); Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDC73 p.Gln14Arg (c.41A>G)?

CDC73 p.Gln14Arg (c.41A>G) is associated with hereditary neoplastic syndrome, parathyroid gland carcinoma (ClinVar).

How common is CDC73 p.Gln14Arg (c.41A>G) in the general population?

CDC73 p.Gln14Arg (c.41A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CDC73 p.Gln14Arg (c.41A>G)?

AlphaMissense predicts ambiguous (score 0.4021) — an in-silico prediction, not a clinical call.

CDC73 p.Gln14Arg

c.41A>G · rs767638609 · VCV838171

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4021 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4021	ambiguous
REVEL	0.27	benign-leaning
SaProt	LLR -9.93	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 16 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	23.4	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

Grpmax group 0.00223% East Asian · 1/44,866 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 8/1,461,838 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,866
European (non-Finnish)	0.000593%	168,573

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.Gln14Arg
Coding: c.41A>G
MANE Select: NM_024529
dbSNP: rs767638609
Type: single nucleotide variant
Location: chr1:193122241 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.94 · 21 PDB
Residue 14: 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.Gln14Pro Uncertain significance ★★ ⚠ same residue
CDC73 p.Gln14Ter 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-gln14arg (accessed [today's date]).

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