Is SBF2 p.Ile1365= (c.4095C>T) pathogenic?

SBF2 p.Ile1365= (c.4095C>T) is classified Likely benign in SBF2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-11-11). Ultra-rare (popmax 0.018%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SBF2 p.Ile1365= (c.4095C>T)?

SBF2 p.Ile1365= (c.4095C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Ile1365= (c.4095C>T) in the general population?

SBF2 p.Ile1365= (c.4095C>T) is ultra-rare (popmax 0.018%, nfe) (gnomAD).

SBF2 p.Ile1365=

c.4095C>T · rs142904756 · VCV514657

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.187	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -4.7, phastCons 1
Overall
CADD	3.988	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.018% European (non-Finnish) · 212/1,180,048 alleles

Filtering AF 0.016% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.0134% 217/1,614,108 alleles · ultra-rare exomes 202/1,461,884 · genomes 15/152,224 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.018%	5,566
Remaining individualsnot grpmax-eligible	0.0064%	15,623
African / African-American	0.00133%	74,940

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.Ile1365=
Coding: c.4095C>T
MANE Select: NM_030962
dbSNP: rs142904756
Type: single nucleotide variant
Location: chr11:9812592 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 1365: the myotubularin phosphatase domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 4

Similar variants

SBF2 p.Ile1365Leu Uncertain significance ★★ ⚠ same residue
SBF2 p.Ile1365Ser Uncertain significance ★ ⚠ same residue
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-ile1365 (accessed [today's date]).

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