Is CCNB1 p.Thr6Ser (c.17C>G) pathogenic?

CCNB1 p.Thr6Ser (c.17C>G) is classified Uncertain significance in CCNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.2625); Ultra-rare (popmax 0.0399%, nfe).

How common is CCNB1 p.Thr6Ser (c.17C>G) in the general population?

CCNB1 p.Thr6Ser (c.17C>G) is ultra-rare (popmax 0.0399%, nfe) (gnomAD).

What do computational predictors say about CCNB1 p.Thr6Ser (c.17C>G)?

AlphaMissense predicts likely benign (score 0.2625) — an in-silico prediction, not a clinical call.

CCNB1 p.Thr6Ser

c.17C>G · rs369118449 · VCV2591489

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2625 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0399%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2625	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -10.06	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 10 kb · p 0.055 · regional, not allelic
Overall
CADD	23.4	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 0.0399% European (non-Finnish) · 466/1,167,924 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0356%

Overall 0.0311% 492/1,584,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0399%	2,506
Remaining individualsnot grpmax-eligible	0.0229%	4,375
African / African-American	0.00676%	14,790
Finnishnot grpmax-eligible	0.00669%	14,948
Admixed American	0.00535%	18,705

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.Thr6Ser
Coding: c.17C>G
MANE Select: NM_031966
dbSNP: rs369118449
Type: single nucleotide variant
Location: chr5:69167279 (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-thr6ser (accessed [today's date]).

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