Is CCNB3 p.Lys846Arg (c.2537A>G) pathogenic?

CCNB3 p.Lys846Arg (c.2537A>G) is classified Uncertain significance in CCNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely benign (0.1216); Rare (popmax 0.243%, afr).

How common is CCNB3 p.Lys846Arg (c.2537A>G) in the general population?

CCNB3 p.Lys846Arg (c.2537A>G) is rare (popmax 0.243%, afr) (gnomAD).

What do computational predictors say about CCNB3 p.Lys846Arg (c.2537A>G)?

AlphaMissense predicts likely benign (score 0.1216) — an in-silico prediction, not a clinical call.

CCNB3 p.Lys846Arg

c.2537A>G · VCV3487376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1216 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.243%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1216	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -10.29	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 -2.6	GERP -1
Regional constraint	o/e 1.02	unconstrained · MANE · 26 kb · p 0.71 · regional, not allelic
Overall
CADD	4.418	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 0.243% African / African-American · 139/57,166 alleles

Filtering AF 0.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.198%

Overall 0.0128% 155/1,209,042 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.243%	411
Middle Eastern	0.023%	4,343
Remaining individualsnot grpmax-eligible	0.0147%	6,797
Admixed American	0.00658%	15,196
South Asian	0.00531%	18,845
European (non-Finnish)	0.000223%	447,441

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.Lys846Arg
Coding: c.2537A>G
MANE Select: NM_033031
Type: single nucleotide variant
Location: chrX:50310706 (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-lys846arg (accessed [today's date]).

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