Is CBFB p.Pro100fs (c.295_296dup) pathogenic?

CBFB p.Pro100fs (c.295296dup) is classified Uncertain significance in CBFB (ClinVar, Single submitter, 2 submitters; last evaluated 2019-07-26). No gnomAD frequency available for this variant; Associated with acute myeloid leukemia.

What condition is associated with CBFB p.Pro100fs (c.295_296dup)?

CBFB p.Pro100fs (c.295_296dup) is associated with acute myeloid leukemia, cleidocranial dysplasia 2 (ClinVar).

How common is CBFB p.Pro100fs (c.295_296dup) in the general population?

CBFB p.Pro100fs (c.295_296dup) is no gnomAD frequency available for this variant (gnomAD).

CBFB p.Pro100fs

c.295_296dup · rs1961069899 · VCV930504

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

acute myeloid leukemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3	GERP 0.83, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CBFB
Protein: p.Pro100fs
Coding: c.295_296dup
MANE Select: NM_022845
dbSNP: rs1961069899
Type: Duplication
Location: chr16:67066693 (GRCh38)
Gene constraint: LOEUF 1.065 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.81 · 22 PDB
Residue 100: a β-strand; a UniProt-annotated variant site (in clcd2); a UniProt-annotated variant site (in a breast cancer sample; somatic mutation)

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

Disease context

acute myeloid leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cleidocranial dysplasia 2

Similar variants

CBFB c.283-2A>G Uncertain significance ★ same condition
CBFB p.Arg83Ter Uncertain significance ★ same condition
CBFB c.283-1039_400-7568del Pathogenic same condition
CBFB c.78+1G>T Pathogenic same condition
CBFB c.*2dup Likely benign 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/cbfb-p-pro100fs (accessed [today's date]).

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