Is CCNB1 p.Ala176Val (c.527C>T) pathogenic?

CCNB1 p.Ala176Val (c.527C>T) is classified Uncertain significance in CCNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: likely benign (0.0932); Absent from gnomAD v4.1.

How common is CCNB1 p.Ala176Val (c.527C>T) in the general population?

CCNB1 p.Ala176Val (c.527C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNB1 p.Ala176Val (c.527C>T)?

AlphaMissense predicts likely benign (score 0.0932) — an in-silico prediction, not a clinical call.

CCNB1 p.Ala176Val

c.527C>T · VCV3264524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0932 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0932	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.1, phastCons 0.002
Regional constraint	o/e 0.92	unconstrained · MANE · 10 kb · p 0.055 · regional, not allelic
Overall
CADD	18.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: CCNB1
Protein: p.Ala176Val
Coding: c.527C>T
MANE Select: NM_031966
Type: single nucleotide variant
Location: chr5:69171433 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.58 · 17 PDB
Residue 176: an α-helix; the 'interaction with cdk2' region

Full CCNB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNB1 p.Ala203Thr Uncertain significance ★★ ⚠ same type
CCNB1 p.Ala125Ser Uncertain significance ★ ⚠ same type
CCNB1 p.Ala152Val Uncertain significance ★ ⚠ same type
CCNB1 p.Ala17Thr Uncertain significance ★ ⚠ same type
CCNB1 p.Ala22Thr Uncertain significance ★ ⚠ same type
CCNB1 p.Ala24Val Uncertain significance ★ ⚠ same type
CCNB1 p.Ala348Thr Uncertain significance ★ ⚠ same type
CCNB1 p.Arg195Trp 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/ccnb1-p-ala176val (accessed [today's date]).

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