Is CCNB3 p.Ser42Pro (c.124T>C) pathogenic?

CCNB3 p.Ser42Pro (c.124T>C) is classified Uncertain significance in CCNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.1807); Ultra-rare (popmax 0.0475%, eas).

How common is CCNB3 p.Ser42Pro (c.124T>C) in the general population?

CCNB3 p.Ser42Pro (c.124T>C) is ultra-rare (popmax 0.0475%, eas) (gnomAD).

What do computational predictors say about CCNB3 p.Ser42Pro (c.124T>C)?

AlphaMissense predicts likely benign (score 0.1807) — an in-silico prediction, not a clinical call.

CCNB3 p.Ser42Pro

c.124T>C · rs201444246 · VCV2590962

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1807 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0475%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1807	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -2, phastCons 0.006
Regional constraint	o/e 1.02	unconstrained · MANE · 26 kb · p 0.71 · regional, not allelic
Overall
CADD	11.13	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0475% East Asian · 16/33,679 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0243%

Overall 0.00141% 17/1,205,309 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0475%	2,105
Remaining individualsnot grpmax-eligible	0.00211%	47,445

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: CCNB3
Protein: p.Ser42Pro
Coding: c.124T>C
MANE Select: NM_033031
dbSNP: rs201444246
Type: single nucleotide variant
Location: chrX:50288807 (GRCh38)
Structure: AlphaFold pLDDT 42.25
Residue 42: the 'disordered' region

Full CCNB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNB3 p.Ala702= Benign ★★ same type
CCNB3 p.Gly1001Arg Benign ★★ same type
CCNB3 p.Lys857Gln Likely benign ★★ ⚠ same type
CCNB3 p.Ser188Thr Benign ★★ ⚠ same type
CCNB3 p.Ala1208Thr Uncertain significance ★ ⚠ same type
CCNB3 p.Ala312Pro Uncertain significance ★ ⚠ same type
CCNB3 p.Ala437Ser Uncertain significance ★ ⚠ same type
CCNB3 p.Ala981Thr 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/ccnb3-p-ser42pro (accessed [today's date]).

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