Is SBF2 p.Ala575= (c.1725A>C) pathogenic?

SBF2 p.Ala575= (c.1725A>C) is classified Likely benign in SBF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-15). Ultra-rare (popmax 0.0329%, mid); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with SBF2 p.Ala575= (c.1725A>C)?

SBF2 p.Ala575= (c.1725A>C) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Ala575= (c.1725A>C) in the general population?

SBF2 p.Ala575= (c.1725A>C) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

SBF2 p.Ala575=

c.1725A>C · rs144514407 · VCV699911

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.002	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -4.4
Overall
CADD	6.461	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00279% 45/1,613,958 alleles · ultra-rare exomes 42/1,461,812 · genomes 3/152,146 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Admixed American	0.00833%	12,001
South Asian	0.00329%	30,363
European (non-Finnish)	0.00288%	34,706
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Ala575=
Coding: c.1725A>C
MANE Select: NM_030962
dbSNP: rs144514407
Type: single nucleotide variant
Location: chr11:9962092 (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

Similar variants

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
SBF2 c.3652+5G>A 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-ala575 (accessed [today's date]).

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