Is SBF2 p.Gln43= (c.129G>A) pathogenic?

SBF2 p.Gln43= (c.129G>A) is classified Conflicting classifications of pathogenicity in SBF2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-17). Ultra-rare (popmax 0.0138%, nfe); Associated with Charcot-Marie-Tooth disease type 4B2.

What condition is associated with SBF2 p.Gln43= (c.129G>A)?

SBF2 p.Gln43= (c.129G>A) is associated with Charcot-Marie-Tooth disease type 4B2, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Gln43= (c.129G>A) in the general population?

SBF2 p.Gln43= (c.129G>A) is ultra-rare (popmax 0.0138%, nfe) (gnomAD).

How is Charcot-Marie-Tooth disease type 4B2 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SBF2 p.Gln43=

c.129G>A · rs761285505 · VCV301928

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0138%, nfe)

Conditions

Charcot-Marie-Tooth disease type 4B2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.55	GERP 0.77, phastCons 1
Overall
CADD	7.382	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0138% European (non-Finnish) · 163/1,177,070 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.0106% 170/1,610,608 alleles · ultra-rare exomes 165/1,458,458 · genomes 5/152,150 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0138%	7,221
Remaining individualsnot grpmax-eligible	0.00641%	15,592
African / African-American	0.00401%	24,933

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: SBF2
Protein: p.Gln43=
Coding: c.129G>A
MANE Select: NM_030962
dbSNP: rs761285505
Type: single nucleotide variant
Location: chr11:10193914 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 43: the udenn domain

Full SBF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 4B2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 4

For Charcot-Marie-Tooth disease type 4B2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

SBF2 p.Gln43Arg Uncertain significance ★ ⚠ same residue
SBF2 c.1601-2A>G Pathogenic/Likely pathogenic ★★ same condition
SBF2 c.3653-1G>A Likely pathogenic ★★ same condition
SBF2 p.Arg342Ter Pathogenic/Likely pathogenic ★★ same condition
SBF2 p.Arg356Ter Pathogenic ★★ same condition
SBF2 p.Arg487Ter Pathogenic ★★ same condition
SBF2 p.Arg77Ter Pathogenic ★★ same condition
SBF2 c.1601-3T>G Uncertain significance ★★ same condition

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/sbf2-p-gln43 (accessed [today's date]).

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