Is SBF2 p.Phe31= (c.93T>C) pathogenic?

SBF2 p.Phe31= (c.93T>C) is classified Benign/Likely benign in SBF2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-19). Low-frequency (popmax 3.06%, sas); Associated with Charcot-Marie-Tooth disease type 4B2.

What condition is associated with SBF2 p.Phe31= (c.93T>C)?

SBF2 p.Phe31= (c.93T>C) is associated with Charcot-Marie-Tooth disease type 4B2, Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Phe31= (c.93T>C) in the general population?

SBF2 p.Phe31= (c.93T>C) is low-frequency (popmax 3.06%, sas) (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.Phe31=

c.93T>C · rs200263159 · VCV301929

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.06%, sas)

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 6.1	GERP 0.56, phastCons 1
Overall
CADD	11.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.06% South Asian · 2,786/91,040 alleles

Filtering AF 2.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.93%

Overall 0.183% 2,946/1,613,064 alleles · low-frequency exomes 2,777/1,460,718 · genomes 169/152,346 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	3.06%	33
Remaining individualsnot grpmax-eligible	0.2%	500
Middle Eastern	0.132%	757
Admixed American	0.005%	20,007
African / African-American	0.00267%	37,521
East Asian	0.00223%	44,800
European (non-Finnish)	0.00178%	56,149

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.Phe31=
Coding: c.93T>C
MANE Select: NM_030962
dbSNP: rs200263159
Type: single nucleotide variant
Location: chr11:10193950 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 31: 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 Charcot-Marie-Tooth disease type 4

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

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

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
SBF2 c.3111-3T>C 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-phe31 (accessed [today's date]).

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