Is SBF2 p.Ile950= (c.2850C>T) pathogenic?

SBF2 p.Ile950= (c.2850C>T) is classified Benign in SBF2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-28). Common (popmax 5.45%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Charcot-Marie-Tooth disease.

What condition is associated with SBF2 p.Ile950= (c.2850C>T)?

SBF2 p.Ile950= (c.2850C>T) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 4B2, Charcot-Marie-Tooth disease type 4 (ClinVar).

SBF2 p.Ile950=

Q: How common is SBF2 p.Ile950= (c.2850C>T) in the general population?

SBF2 p.Ile950= (c.2850C>T) is common (popmax 5.45%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2850C>T · rs74642088 · VCV306592

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 5.45%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Charcot-Marie-Tooth disease

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 3.9	GERP 1.3, phastCons 1
Overall
CADD	9.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.45% African / African-American · 4,088/75,006 alleles

Filtering AF 5.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.25%

Overall 0.307% 4,957/1,613,772 alleles · common exomes 2,660/1,461,520 · genomes 2,297/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.45%	18
Middle Eastern	0.776%	129
Remaining individualsnot grpmax-eligible	0.429%	233
Admixed American	0.393%	254
European (non-Finnish)	0.0247%	4,054
Ashkenazi Jewishnot grpmax-eligible	0.0237%	4,228
South Asian	0.0209%	4,794
Finnishnot grpmax-eligible	0.00156%	64,032

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.Ile950=
Coding: c.2850C>T
MANE Select: NM_030962
dbSNP: rs74642088
Type: single nucleotide variant
Location: chr11:9847040 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 950: the gram domain

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

Disease context

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

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

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-ile950 (accessed [today's date]).

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