Is CCNB2 p.Ser274= (c.822A>G) pathogenic?

CCNB2 p.Ser274= (c.822A>G) is classified Likely benign in CCNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Very rare (popmax 0.00348%, nfe).

How common is CCNB2 p.Ser274= (c.822A>G) in the general population?

CCNB2 p.Ser274= (c.822A>G) is very rare (popmax 0.00348%, nfe) (gnomAD).

CCNB2 p.Ser274=

c.822A>G · rs754577593 · VCV2645382

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00348%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.6	GERP -7.3
Overall
CADD	0.489	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00348% European (non-Finnish) · 41/1,179,360 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.0026% 42/1,613,276 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00348%	28,765
Remaining individualsnot grpmax-eligible	0.0016%	62,452

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: CCNB2
Protein: p.Ser274=
Coding: c.822A>G
MANE Select: NM_004701
dbSNP: rs754577593
Type: single nucleotide variant
Location: chr15:59116914 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.14

Full CCNB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNB2 p.Ile395Thr Benign ★★ same type
CCNB2 p.Lys89= Benign ★★ same type
CCNB2 p.Met100Thr Benign ★★ same type
CCNB2 p.Ala112Gly Uncertain significance ★ ⚠ same type
CCNB2 p.Ala167Thr Uncertain significance ★ ⚠ same type
CCNB2 p.Ala46Thr Uncertain significance ★ ⚠ same type
CCNB2 p.Arg164Cys Uncertain significance ★ ⚠ same type
CCNB2 p.Arg164His 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/ccnb2-p-ser274 (accessed [today's date]).

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