Is CCNB2 p.Asp232Ala (c.695A>C) pathogenic?

CCNB2 p.Asp232Ala (c.695A>C) is classified Uncertain significance in CCNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-02). AlphaMissense: likely pathogenic (0.9468); Absent from gnomAD v4.1.

How common is CCNB2 p.Asp232Ala (c.695A>C) in the general population?

CCNB2 p.Asp232Ala (c.695A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNB2 p.Asp232Ala (c.695A>C)?

AlphaMissense predicts likely pathogenic (score 0.9468) — an in-silico prediction, not a clinical call.

CCNB2 p.Asp232Ala

c.695A>C · rs2541949910 · VCV2331960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9468 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9468	likely pathogenic
REVEL	0.69	pathogenic-leaning
SaProt	LLR -10.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCNB2
Protein: p.Asp232Ala
Coding: c.695A>C
MANE Select: NM_004701
dbSNP: rs2541949910
Type: single nucleotide variant
Location: chr15:59116787 (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-asp232ala (accessed [today's date]).

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