Is SBF1 p.His693= (c.2079C>T) pathogenic?

SBF1 p.His693= (c.2079C>T) is classified Benign/Likely benign in SBF1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-06-01). Rare (popmax 0.317%, nfe); Associated with Charcot-Marie-Tooth disease type 4B3.

What condition is associated with SBF1 p.His693= (c.2079C>T)?

SBF1 p.His693= (c.2079C>T) is associated with Charcot-Marie-Tooth disease type 4B3 (ClinVar).

How common is SBF1 p.His693= (c.2079C>T) in the general population?

SBF1 p.His693= (c.2079C>T) is rare (popmax 0.317%, nfe) (gnomAD).

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.His693=

c.2079C>T · rs199672732 · VCV774363

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.317%, nfe)

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 1	GERP -5.2, phastCons 1
Overall
CADD	5.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.317% European (non-Finnish) · 3,743/1,179,712 alleles

Filtering AF 0.309% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.305%

Overall 0.247% 3,983/1,612,560 alleles · rare exomes 3,714/1,460,232 · genomes 269/152,328 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.317%	315
Remaining individualsnot grpmax-eligible	0.184%	543
Finnishnot grpmax-eligible	0.084%	1,190
Admixed American	0.0634%	1,577
African / African-American	0.0386%	2,588
Middle Eastern	0.033%	3,026
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,580
South Asian	0.0022%	45,478

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.His693=
Coding: c.2079C>T
MANE Select: NM_002972
dbSNP: rs199672732
Type: single nucleotide variant
Location: chr22:50462607 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72

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 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
SBF1 p.Ala913Thr Uncertain significance ★★ ⚠ same condition
SBF1 p.Arg1323Trp 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-his693 (accessed [today's date]).

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