Is CCNB2 p.Thr285Ala (c.853A>G) pathogenic?

CCNB2 p.Thr285Ala (c.853A>G) is classified Uncertain significance in CCNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely benign (0.2018); Very rare (popmax 0.00668%, afr).

How common is CCNB2 p.Thr285Ala (c.853A>G) in the general population?

CCNB2 p.Thr285Ala (c.853A>G) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about CCNB2 p.Thr285Ala (c.853A>G)?

AlphaMissense predicts likely benign (score 0.2018) — an in-silico prediction, not a clinical call.

CCNB2 p.Thr285Ala

c.853A>G · VCV4222038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2018 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2018	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -11.70	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 20 kb · p 0.94 · regional, not allelic
Overall
CADD	26.4	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 0.00668% African / African-American · 5/74,898 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00143% 23/1,612,898 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,980
Remaining individualsnot grpmax-eligible	0.00321%	31,196
East Asian	0.00223%	44,888
Admixed American	0.00167%	59,994
European (non-Finnish)	0.0011%	90,766
South Asian	0.0011%	91,032

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.Thr285Ala
Coding: c.853A>G
MANE Select: NM_004701
Type: single nucleotide variant
Location: chr15:59117246 (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-thr285ala (accessed [today's date]).

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