Is SBF2 p.Phe215= (c.645T>C) pathogenic?

SBF2 p.Phe215= (c.645T>C) is classified Benign/Likely benign in SBF2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.5%, afr); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with SBF2 p.Phe215= (c.645T>C)?

SBF2 p.Phe215= (c.645T>C) is associated with Charcot-Marie-Tooth disease type 4, Charcot-Marie-Tooth disease type 4B2 (ClinVar).

How common is SBF2 p.Phe215= (c.645T>C) in the general population?

SBF2 p.Phe215= (c.645T>C) is low-frequency (popmax 1.5%, afr) (gnomAD).

SBF2 p.Phe215=

c.645T>C · rs148187321 · VCV301872

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.5%, afr)

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.37	GERP -3.1, phastCons 0.52
Overall
CADD	7.541	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.5% African / African-American · 1,125/75,036 alleles

Filtering AF 1.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4%

Overall 0.109% 1,757/1,613,514 alleles · low-frequency exomes 1,074/1,461,178 · genomes 683/152,336 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.5%	67
Ashkenazi Jewishnot grpmax-eligible	0.933%	107
Remaining individualsnot grpmax-eligible	0.283%	353
Middle Eastern	0.116%	865
Admixed American	0.0933%	1,072
South Asian	0.00988%	10,119
European (non-Finnish)	0.0089%	11,233
East Asian	0.00223%	44,790
Finnishnot grpmax-eligible	0.00156%	64,040

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.Phe215=
Coding: c.645T>C
MANE Select: NM_030962
dbSNP: rs148187321
Type: single nucleotide variant
Location: chr11:10002664 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 215: the cdenn domain

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

Disease context

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

Also linked: Charcot-Marie-Tooth disease type 4B2

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-phe215 (accessed [today's date]).

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