Is CBFB p.Arg147Gly (c.439C>G) pathogenic?

CBFB p.Arg147Gly (c.439C>G) is classified Uncertain significance in CBFB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: likely pathogenic (0.8116); Very rare (popmax 0.00051%, nfe).

How common is CBFB p.Arg147Gly (c.439C>G) in the general population?

CBFB p.Arg147Gly (c.439C>G) is very rare (popmax 0.00051%, nfe) (gnomAD).

What do computational predictors say about CBFB p.Arg147Gly (c.439C>G)?

AlphaMissense predicts likely pathogenic (score 0.8116) — an in-silico prediction, not a clinical call.

CBFB p.Arg147Gly

c.439C>G · rs1961582722 · VCV2473963

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8116 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00051%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8116	likely pathogenic
REVEL	0.236	benign-leaning
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 69 kb · p 2.2e-06 · regional, not allelic
Overall
CADD	25.0	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 0.00051% European (non-Finnish) · 6/1,177,146 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000373% 6/1,609,934 alleles · very rare

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: CBFB
Protein: p.Arg147Gly
Coding: c.439C>G
MANE Select: NM_022845
dbSNP: rs1961582722
Type: single nucleotide variant
Location: chr16:67082252 (GRCh38)
Gene constraint: LOEUF 1.065 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.81 · 22 PDB
Residue 147: an α-helix; a UniProt-annotated variant site (in clcd2)

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

Similar variants

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
CBFB c.283-2A>G Uncertain significance ★ same type
CBFB c.399+2T>C Uncertain significance ★ same type
CBFB p.Arg83Ter Uncertain significance ★ same type
CBFB p.Gln45His 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/cbfb-p-arg147gly (accessed [today's date]).

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