Is CCNB3 p.Val1369Ile (c.4105G>A) pathogenic?

CCNB3 p.Val1369Ile (c.4105G>A) is classified Uncertain significance in CCNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). AlphaMissense: likely benign (0.2965); Ultra-rare (popmax 0.0231%, nfe).

How common is CCNB3 p.Val1369Ile (c.4105G>A) in the general population?

CCNB3 p.Val1369Ile (c.4105G>A) is ultra-rare (popmax 0.0231%, nfe) (gnomAD).

What do computational predictors say about CCNB3 p.Val1369Ile (c.4105G>A)?

AlphaMissense predicts likely benign (score 0.2965) — an in-silico prediction, not a clinical call.

CCNB3 p.Val1369Ile

c.4105G>A · rs782056499 · VCV2525331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2965 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2965	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -10.11	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 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 41 kb · p 5.1e-07 · regional, not allelic
Overall
CADD	22.7	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 0.0231% European (non-Finnish) · 207/894,869 alleles

Filtering AF 0.0205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0195%

Overall 0.0177% 214/1,209,410 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0231%	4,323
Remaining individualsnot grpmax-eligible	0.0126%	7,929
African / African-American	0.00175%	57,118

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: CCNB3
Protein: p.Val1369Ile
Coding: c.4105G>A
MANE Select: NM_033031
dbSNP: rs782056499
Type: single nucleotide variant
Location: chrX:50351620 (GRCh38)
Structure: AlphaFold pLDDT 42.25

Full CCNB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNB3 p.Ala702= Benign ★★ same type
CCNB3 p.Gly1001Arg Benign ★★ same type
CCNB3 p.Lys857Gln Likely benign ★★ ⚠ same type
CCNB3 p.Ser188Thr Benign ★★ ⚠ same type
CCNB3 p.Ala1208Thr Uncertain significance ★ ⚠ same type
CCNB3 p.Ala312Pro Uncertain significance ★ ⚠ same type
CCNB3 p.Ala437Ser Uncertain significance ★ ⚠ same type
CCNB3 p.Ala981Thr 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/ccnb3-p-val1369ile (accessed [today's date]).

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