Is SBF1 p.Pro1340= (c.4020C>T) pathogenic?

SBF1 p.Pro1340= (c.4020C>T) is classified Benign in SBF1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 8.49%, mid) — too common for a highly-penetrant pathogenic allele; Associated with Charcot-Marie-Tooth disease type 4B3.

What condition is associated with SBF1 p.Pro1340= (c.4020C>T)?

SBF1 p.Pro1340= (c.4020C>T) is associated with Charcot-Marie-Tooth disease type 4B3 (ClinVar).

How is Charcot-Marie-Tooth disease type 4B3 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SBF1 p.Pro1340=

Q: How common is SBF1 p.Pro1340= (c.4020C>T) in the general population?

SBF1 p.Pro1340= (c.4020C>T) is common (popmax 8.49%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4020C>T · rs79468232 · VCV811559

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 8.49%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

Charcot-Marie-Tooth disease type 4B3

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 -5.5	GERP -4.7
Overall
CADD	0.293	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49% Middle Eastern · 501/5,902 alleles

Filtering AF 7.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.63%

Overall 5.26% 83,223/1,582,504 alleles · common exomes 75,485/1,430,544 · genomes 7,738/151,960 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	8.49%	12
Ashkenazi Jewishnot grpmax-eligible	7.58%	13
South Asian	6.8%	15
Finnishnot grpmax-eligible	6.63%	15
Remaining individualsnot grpmax-eligible	5.37%	19
European (non-Finnish)	5.31%	19
African / African-American	5.3%	19
Amishnot grpmax-eligible	4.41%	23
Admixed American	2.88%	35
East Asian	0.0114%	8,795

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: SBF1
Protein: p.Pro1340=
Coding: c.4020C>T
MANE Select: NM_002972
dbSNP: rs79468232
Type: single nucleotide variant
Location: chr22:50456558 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 1340: the myotubularin phosphatase domain

Full SBF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 4B3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Charcot-Marie-Tooth disease type 4B3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

SBF1 p.Pro1340Ser Uncertain significance ★ ⚠ same residue
SBF1 p.Pro1340Leu Benign ★ same residue
SBF1 c.3826+1G>A Pathogenic/Likely pathogenic ★★ same condition
SBF1 p.Met417Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
SBF1 c.4554+6C>T Uncertain significance ★★ same condition
SBF1 p.Ala1258Thr Uncertain significance ★★ ⚠ same condition
SBF1 p.Ala1836Gly Uncertain significance ★★ ⚠ same condition
SBF1 p.Ala1836Val 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/sbf1-p-pro1340 (accessed [today's date]).

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