Is CDC123 p.Pro84Ser (c.250C>T) pathogenic?

CDC123 p.Pro84Ser (c.250C>T) is classified Uncertain significance in CDC123 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.2959); Very rare (popmax 0.00339%, amr).

How common is CDC123 p.Pro84Ser (c.250C>T) in the general population?

CDC123 p.Pro84Ser (c.250C>T) is very rare (popmax 0.00339%, amr) (gnomAD).

What do computational predictors say about CDC123 p.Pro84Ser (c.250C>T)?

AlphaMissense predicts likely benign (score 0.2959) — an in-silico prediction, not a clinical call.

CDC123 p.Pro84Ser

c.250C>T · VCV3488273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00339%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2959	likely benign
REVEL	0.65	pathogenic-leaning
SaProt	LLR -8.37	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.012 · regional, not allelic
Overall
CADD	27.4	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 0.00339% Admixed American · 2/59,034 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00174% 28/1,608,932 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00339%	29,517
Remaining individualsnot grpmax-eligible	0.00321%	31,121
European (non-Finnish)	0.00195%	51,213
African / African-American	0.00134%	74,572

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: CDC123
Protein: p.Pro84Ser
Coding: c.250C>T
MANE Select: NM_006023
Type: single nucleotide variant
Location: chr10:12215752 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.82 · 2 PDB
Residue 84: an α-helix

Full CDC123 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC123 c.489+3A>C Benign ★★ same type
CDC123 c.847-4A>G Benign ★★ same type
CDC123 p.Ala113Val Uncertain significance ★ ⚠ same type
CDC123 p.Ala279Thr Uncertain significance ★ ⚠ same type
CDC123 p.Ala319Thr Uncertain significance ★ ⚠ same type
CDC123 p.Arg142Gly Uncertain significance ★ ⚠ same type
CDC123 p.Arg142His Uncertain significance ★ ⚠ same type
CDC123 p.Arg167Gln Uncertain significance ★ ⚠ same type

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/cdc123-p-pro84ser (accessed [today's date]).

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