Is SBF2 p.Arg600Gln (c.1799G>A) pathogenic?

SBF2 p.Arg600Gln (c.1799G>A) is classified Uncertain significance in SBF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-08). AlphaMissense: likely benign (0.2164); Very rare (popmax 0.00483%, nfe); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with SBF2 p.Arg600Gln (c.1799G>A)?

SBF2 p.Arg600Gln (c.1799G>A) is associated with Charcot-Marie-Tooth disease type 4, Charcot-Marie-Tooth disease type 4B2 (ClinVar).

How common is SBF2 p.Arg600Gln (c.1799G>A) in the general population?

SBF2 p.Arg600Gln (c.1799G>A) is very rare (popmax 0.00483%, nfe) (gnomAD).

What do computational predictors say about SBF2 p.Arg600Gln (c.1799G>A)?

AlphaMissense predicts likely benign (score 0.2164) — an in-silico prediction, not a clinical call.

SBF2 p.Arg600Gln

c.1799G>A · rs185968327 · VCV306604

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2164 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00483%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
AlphaMissense	0.2164	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -5.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 514 kb · p 7.7e-06 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00483% European (non-Finnish) · 57/1,179,878 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00409% 66/1,613,966 alleles · very rare exomes 62/1,461,694 · genomes 4/152,272 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00483%	20,700
East Asian	0.00446%	22,432
African / African-American	0.004%	25,009
Remaining individualsnot grpmax-eligible	0.0032%	31,252
Admixed American	0.00167%	60,028
South Asian	0.0011%	91,078

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.Arg600Gln
Coding: c.1799G>A
MANE Select: NM_030962
dbSNP: rs185968327
Type: single nucleotide variant
Location: chr11:9962018 (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

Similar variants

SBF2 p.Arg600Trp Uncertain significance ★ ⚠ 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.Arg487Ter 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-arg600gln (accessed [today's date]).

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