Is SBF2 p.Arg1823= (c.5469T>C) pathogenic?

SBF2 p.Arg1823= (c.5469T>C) is classified Likely benign in SBF2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-24). Ultra-rare (popmax 0.0264%, sas); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with SBF2 p.Arg1823= (c.5469T>C)?

SBF2 p.Arg1823= (c.5469T>C) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Arg1823= (c.5469T>C) in the general population?

SBF2 p.Arg1823= (c.5469T>C) is ultra-rare (popmax 0.0264%, sas) (gnomAD).

SBF2 p.Arg1823=

c.5469T>C · rs373457270 · VCV701568

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0264%, sas)

Conditions

Charcot-Marie-Tooth disease type 4

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 · A>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP -1.8, phastCons 1
Overall
CADD	7.499	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0264% South Asian · 24/91,078 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0154%

Overall 0.00211% 34/1,614,106 alleles · ultra-rare exomes 34/1,461,864 · genomes 0/152,242 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0264%	3,795
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.00333%	30,011
African / African-American	0.00133%	75,022
European (non-Finnish)	8.47e-05%	1,179,999

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.Arg1823=
Coding: c.5469T>C
MANE Select: NM_030962
dbSNP: rs373457270
Type: single nucleotide variant
Location: chr11:9780499 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 1823: the ph 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.Arg1823His Uncertain significance ★★ ⚠ same residue
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
SBF2 c.3111-3T>C 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-arg1823 (accessed [today's date]).

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