Is CCNB1 p.His304Pro (c.911A>C) pathogenic?

CCNB1 p.His304Pro (c.911A>C) is classified Uncertain significance in CCNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely pathogenic (0.7976); Very rare (popmax 8.48e-05%, nfe).

How common is CCNB1 p.His304Pro (c.911A>C) in the general population?

CCNB1 p.His304Pro (c.911A>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CCNB1 p.His304Pro (c.911A>C)?

AlphaMissense predicts likely pathogenic (score 0.7976) — an in-silico prediction, not a clinical call.

CCNB1 p.His304Pro

c.911A>C · VCV3487357

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7976 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7976	likely pathogenic
REVEL	0.346	indeterminate
SaProt	LLR -12.81	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 10 kb · p 0.055 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,736 alleles

Overall 6.84e-05% 1/1,461,464 alleles · very rare

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: CCNB1
Protein: p.His304Pro
Coding: c.911A>C
MANE Select: NM_031966
Type: single nucleotide variant
Location: chr5:69175082 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.58 · 17 PDB
Residue 304: an α-helix

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.Ala176Val 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

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-his304pro (accessed [today's date]).

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