Is CBFB p.Arg83Ter (c.247C>T) pathogenic?

CBFB p.Arg83Ter (c.247C>T) is classified Uncertain significance in CBFB (ClinVar, Single submitter, 2 submitters; last evaluated 2022-11-14). Absent from gnomAD v4.1; Associated with cleidocranial dysplasia 2.

What condition is associated with CBFB p.Arg83Ter (c.247C>T)?

CBFB p.Arg83Ter (c.247C>T) is associated with cleidocranial dysplasia 2 (ClinVar).

How common is CBFB p.Arg83Ter (c.247C>T) in the general population?

CBFB p.Arg83Ter (c.247C>T) is absent from gnomAD v4.1 (gnomAD).

CBFB p.Arg83Ter

c.247C>T · rs538809858 · VCV1712245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cleidocranial dysplasia 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: CBFB
Protein: p.Arg83Ter
Coding: c.247C>T
MANE Select: NM_022845
dbSNP: rs538809858
Type: single nucleotide variant
Location: chr16:67036720 (GRCh38)
Gene constraint: LOEUF 1.065 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.81 · 22 PDB
Residue 83: a UniProt-annotated variant site (in clcd2)

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

Disease context

cleidocranial dysplasia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CBFB c.283-2A>G Uncertain significance ★ same condition
CBFB c.78+1G>T Pathogenic same condition
CBFB p.Pro100fs Uncertain significance ★ same condition
CBFB c.283-1039_400-7568del Pathogenic same condition
CBFB c.400-206T>C Benign ★★ same type
CBFB c.495+144G>A Benign ★★ same type
CBFB c.78+111G>A Benign ★★ same type
CBFB c.79-18G>T 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-arg83ter (accessed [today's date]).

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