Is SBF2 p.Ala391= (c.1173A>G) pathogenic?

SBF2 p.Ala391= (c.1173A>G) is classified Benign/Likely benign in SBF2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-04-01). Low-frequency (popmax 4.47%, mid); Associated with Inborn genetic diseases.

What condition is associated with SBF2 p.Ala391= (c.1173A>G)?

SBF2 p.Ala391= (c.1173A>G) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4B2, Charcot-Marie-Tooth disease (ClinVar).

How common is SBF2 p.Ala391= (c.1173A>G) in the general population?

SBF2 p.Ala391= (c.1173A>G) is low-frequency (popmax 4.47%, mid) (gnomAD).

SBF2 p.Ala391=

c.1173A>G · rs79470805 · VCV220575

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.47%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.81, phastCons 1
Overall
CADD	10.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.47% Middle Eastern · 270/6,044 alleles

Filtering AF 4.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.86%

Overall 0.891% 14,359/1,610,934 alleles · low-frequency exomes 13,256/1,458,752 · genomes 1,103/152,182 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	4.47%	22
Amishnot grpmax-eligible	2.52%	40
South Asian	1.4%	71
Remaining individualsnot grpmax-eligible	0.97%	103
European (non-Finnish)	0.956%	105
Ashkenazi Jewishnot grpmax-eligible	0.729%	137
Admixed American	0.522%	191
Finnishnot grpmax-eligible	0.405%	247
African / African-American	0.191%	524
East Asian	0.00447%	22,371

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.Ala391=
Coding: c.1173A>G
MANE Select: NM_030962
dbSNP: rs79470805
Type: single nucleotide variant
Location: chr11:9992538 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 391: the ddenn domain

Full SBF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

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
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-ala391 (accessed [today's date]).

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