Is SBF2 p.Phe65fs (c.192_193dup) pathogenic?

SBF2 p.Phe65fs (c.192193dup) is classified Pathogenic in SBF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-15). Very rare (popmax 0.000339%, nfe); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with SBF2 p.Phe65fs (c.192_193dup)?

SBF2 p.Phe65fs (c.192_193dup) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Phe65fs (c.192_193dup) in the general population?

SBF2 p.Phe65fs (c.192_193dup) is very rare (popmax 0.000339%, nfe) (gnomAD).

SBF2 p.Phe65fs

c.192_193dup · rs1949709115 · VCV942856

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 40
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,922 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,046 alleles · very rare exomes 5/1,461,756 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)grpmax	0.000339%	294,981

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe65fs
Coding: c.192_193dup
MANE Select: NM_030962
dbSNP: rs1949709115
Type: Duplication
Location: chr11:10042929 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 65: the udenn 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.Phe65Leu Uncertain significance ★ ⚠ same residue
SBF2 c.142-14dup Benign/Likely benign ★★ same condition
SBF2 p.Arg1433fs Pathogenic ★ same condition
SBF2 p.Ser1397fs Pathogenic ★ same condition
SBF2 p.Thr39fs Pathogenic ★ same condition
SBF2 c.620-10dup Uncertain significance ★ same condition
SBF2 p.Glu1230_Gln1231insProSerSerSerIleGlu Uncertain significance ★ same condition
SBF2 c.862-12dup Benign ★ 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-phe65fs (accessed [today's date]).

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