Is CCNB3 p.Ser230Pro (c.688T>C) pathogenic?

CCNB3 p.Ser230Pro (c.688T>C) is classified Uncertain significance in CCNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.1222); Very rare (popmax 0.00176%, afr).

How common is CCNB3 p.Ser230Pro (c.688T>C) in the general population?

CCNB3 p.Ser230Pro (c.688T>C) is very rare (popmax 0.00176%, afr) (gnomAD).

What do computational predictors say about CCNB3 p.Ser230Pro (c.688T>C)?

AlphaMissense predicts likely benign (score 0.1222) — an in-silico prediction, not a clinical call.

CCNB3 p.Ser230Pro

c.688T>C · VCV3264534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1222 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00176%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1222	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -6.99	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 0.004	GERP -2.2
Regional constraint	o/e 1.02	unconstrained · MANE · 26 kb · p 0.71 · regional, not allelic
Overall
CADD	16.37	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 0.00176% African / African-American · 1/56,941 alleles

Overall 0.000901% 1/110,953 alleles · very rare

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.Ser230Pro
Coding: c.688T>C
MANE Select: NM_033031
Type: single nucleotide variant
Location: chrX:50308857 (GRCh38)
Structure: AlphaFold pLDDT 42.25

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-ser230pro (accessed [today's date]).

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