Is SBF2 p.Ala1376= (c.4128G>A) pathogenic?

SBF2 p.Ala1376= (c.4128G>A) is classified Benign/Likely benign in SBF2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-01). Rare (popmax 0.555%, eas); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with SBF2 p.Ala1376= (c.4128G>A)?

SBF2 p.Ala1376= (c.4128G>A) is associated with Charcot-Marie-Tooth disease type 4, Charcot-Marie-Tooth disease type 4B2 (ClinVar).

How common is SBF2 p.Ala1376= (c.4128G>A) in the general population?

SBF2 p.Ala1376= (c.4128G>A) is rare (popmax 0.555%, eas) (gnomAD).

SBF2 p.Ala1376=

c.4128G>A · rs191964053 · VCV382124

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.555%, eas)

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	0.049	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -5.1
Overall
CADD	4.096	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.555% East Asian · 249/44,882 alleles

Filtering AF 0.498% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.476%

Overall 0.0193% 311/1,614,192 alleles · rare exomes 279/1,461,880 · genomes 32/152,312 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.555%	180
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0448%	2,232
Admixed American	0.0167%	6,002
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
South Asian	0.00329%	30,361
Finnishnot grpmax-eligible	0.00312%	32,014
European (non-Finnish)	0.00127%	78,669

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.Ala1376=
Coding: c.4128G>A
MANE Select: NM_030962
dbSNP: rs191964053
Type: single nucleotide variant
Location: chr11:9812559 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 1376: the myotubularin phosphatase 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

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

Similar variants

SBF2 p.Ala1376Val 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-ala1376 (accessed [today's date]).

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