Is SBF1 p.Val388= (c.1164C>T) pathogenic?

SBF1 p.Val388= (c.1164C>T) is classified Likely benign in SBF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0375%, sas); Associated with Charcot-Marie-Tooth disease type 4B3.

What condition is associated with SBF1 p.Val388= (c.1164C>T)?

SBF1 p.Val388= (c.1164C>T) is associated with Charcot-Marie-Tooth disease type 4B3 (ClinVar).

How common is SBF1 p.Val388= (c.1164C>T) in the general population?

SBF1 p.Val388= (c.1164C>T) is ultra-rare (popmax 0.0375%, sas) (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.Val388=

c.1164C>T · rs376600058 · VCV726469

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0375%, sas)

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	all four deltas below 0.2 · G>C here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.3	GERP -4
Overall
CADD	2.207	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0375% South Asian · 34/90,782 alleles

Filtering AF 0.0275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0242%

Overall 0.0231% 373/1,611,988 alleles · ultra-rare exomes 351/1,459,680 · genomes 22/152,308 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0375%	2,670
European (non-Finnish)	0.0277%	3,607
Remaining individualsnot grpmax-eligible	0.0128%	7,800
African / African-American	0.004%	25,014
Finnishnot grpmax-eligible	0.00158%	63,392

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.Val388=
Coding: c.1164C>T
MANE Select: NM_002972
dbSNP: rs376600058
Type: single nucleotide variant
Location: chr22:50465254 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 388: the ddenn 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.Val388Ile Conflicting classifications of pathogenicity ★ ⚠ 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
SBF1 p.Ala913Thr 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-val388 (accessed [today's date]).

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