Is SBF2 p.Ser1296= (c.3888G>A) pathogenic?

SBF2 p.Ser1296= (c.3888G>A) is classified Conflicting classifications of pathogenicity in SBF2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0683%, amr); Associated with Inborn genetic diseases.

What condition is associated with SBF2 p.Ser1296= (c.3888G>A)?

SBF2 p.Ser1296= (c.3888G>A) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4B2, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Ser1296= (c.3888G>A) in the general population?

SBF2 p.Ser1296= (c.3888G>A) is ultra-rare (popmax 0.0683%, amr) (gnomAD).

SBF2 p.Ser1296=

c.3888G>A · rs375669985 · VCV476928

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0683%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.139	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -4.4
Overall
CADD	5.381	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0683% Admixed American · 41/59,988 alleles

Filtering AF 0.0518% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0459%

Overall 0.01% 162/1,613,958 alleles · ultra-rare exomes 125/1,461,882 · genomes 37/152,076 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0683%	1,463
African / African-American	0.012%	8,319
European (non-Finnish)	0.00881%	11,346
Remaining individualsnot grpmax-eligible	0.008%	12,498
South Asian	0.00329%	30,359

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.Ser1296=
Coding: c.3888G>A
MANE Select: NM_030962
dbSNP: rs375669985
Type: single nucleotide variant
Location: chr11:9816930 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 1296: 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 4B2 Charcot-Marie-Tooth disease type 4

Similar variants

SBF2 p.Ser1296Leu Uncertain significance ★★ ⚠ same residue
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

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-ser1296 (accessed [today's date]).

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