Is SBF2 p.Val1286= (c.3858T>C) pathogenic?

SBF2 p.Val1286= (c.3858T>C) is classified Likely benign in SBF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-01). Ultra-rare (popmax 0.0178%, eas); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with SBF2 p.Val1286= (c.3858T>C)?

SBF2 p.Val1286= (c.3858T>C) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Val1286= (c.3858T>C) in the general population?

SBF2 p.Val1286= (c.3858T>C) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

SBF2 p.Val1286=

c.3858T>C · rs768590614 · VCV1142586

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.047	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.79 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.2	GERP 2.2, phastCons 1
Overall
CADD	10.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,894 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000496% 8/1,614,094 alleles · ultra-rare exomes 5/1,461,890 · genomes 3/152,204 · joint denominator

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.Val1286=
Coding: c.3858T>C
MANE Select: NM_030962
dbSNP: rs768590614
Type: single nucleotide variant
Location: chr11:9816960 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 1286: the myotubularin phosphatase 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

Similar variants

SBF2 p.Val1286Ala Conflicting classifications of pathogenicity ★ ⚠ 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
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-val1286 (accessed [today's date]).

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