Is CCNB1 p.Leu83Phe (c.247C>T) pathogenic?

CCNB1 p.Leu83Phe (c.247C>T) is classified Uncertain significance in CCNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-19). AlphaMissense: likely benign (0.0875); Absent from gnomAD v4.1.

How common is CCNB1 p.Leu83Phe (c.247C>T) in the general population?

CCNB1 p.Leu83Phe (c.247C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNB1 p.Leu83Phe (c.247C>T)?

AlphaMissense predicts likely benign (score 0.0875) — an in-silico prediction, not a clinical call.

CCNB1 p.Leu83Phe

c.247C>T · VCV3487360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0875 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0875	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -9.07	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 0.2	GERP -3.7, phastCons 0.58
Regional constraint	o/e 0.92	unconstrained · MANE · 10 kb · p 0.055 · regional, not allelic
Overall
CADD	18.03	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.Leu83Phe
Coding: c.247C>T
MANE Select: NM_031966
Type: single nucleotide variant
Location: chr5:69168227 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.58 · 17 PDB

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-leu83phe (accessed [today's date]).

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