Is SBF2 p.Arg487Ter (c.1459C>T) pathogenic?

SBF2 p.Arg487Ter (c.1459C>T) is classified Pathogenic in SBF2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-05-02). Very rare (popmax 0.00017%, nfe); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with SBF2 p.Arg487Ter (c.1459C>T)?

SBF2 p.Arg487Ter (c.1459C>T) is associated with Charcot-Marie-Tooth disease type 4, Charcot-Marie-Tooth disease type 4B2, Charcot-Marie-Tooth disease (ClinVar).

How common is SBF2 p.Arg487Ter (c.1459C>T) in the general population?

SBF2 p.Arg487Ter (c.1459C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

SBF2 p.Arg487Ter

c.1459C>T · rs120074139 · VCV2912

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 40
REVEL	0.118	moderately benign-leaning
Splicing
SpliceAI	Δ0.46	donor gain · deltas
Pangolin	Δ0.30	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.1	GERP 1.1, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,912 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,978 alleles · very rare exomes 2/1,461,786 · genomes 0/152,192 · joint denominator

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.Arg487Ter
Coding: c.1459C>T
MANE Select: NM_030962
dbSNP: rs120074139
Type: single nucleotide variant
Location: chr11:9968482 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74

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

Also linked: Charcot-Marie-Tooth disease type 4B2 Charcot-Marie-Tooth disease

Similar variants

SBF2 p.Arg487Gln Uncertain significance ★★ ⚠ same residue
SBF2 p.Arg487= Likely benign ★★ 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.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-arg487ter (accessed [today's date]).

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