Is CCNB3 p.Ser809Arg (c.2427C>A) pathogenic?

CCNB3 p.Ser809Arg (c.2427C>A) is classified Uncertain significance in CCNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.3257); Very rare (popmax 0.00875%, amr).

How common is CCNB3 p.Ser809Arg (c.2427C>A) in the general population?

CCNB3 p.Ser809Arg (c.2427C>A) is very rare (popmax 0.00875%, amr) (gnomAD).

What do computational predictors say about CCNB3 p.Ser809Arg (c.2427C>A)?

AlphaMissense predicts likely benign (score 0.3257) — an in-silico prediction, not a clinical call.

CCNB3 p.Ser809Arg

c.2427C>A · rs781881598 · VCV3139880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3257 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00875%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3257	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -10.44	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.6	GERP -2.9
Regional constraint	o/e 1.02	unconstrained · MANE · 26 kb · p 0.71 · regional, not allelic
Overall
CADD	0.428	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 0.00875% Admixed American · 4/45,729 alleles

Filtering AF 0.00294% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00177%

Overall 0.00231% 28/1,209,894 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00875%	11,432
Remaining individualsnot grpmax-eligible	0.0042%	23,798
European (non-Finnish)	0.00246%	40,692

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.Ser809Arg
Coding: c.2427C>A
MANE Select: NM_033031
dbSNP: rs781881598
Type: single nucleotide variant
Location: chrX:50310596 (GRCh38)
Structure: AlphaFold pLDDT 42.25

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

Similar variants

CCNB3 p.Ser809Asn Uncertain significance ★ ⚠ same residue
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

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-ser809arg (accessed [today's date]).

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