Is SBF1 p.Asp1002= (c.3006C>T) pathogenic?

SBF1 p.Asp1002= (c.3006C>T) is classified Benign in SBF1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Common (popmax 6.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Charcot-Marie-Tooth disease type 4B3.

What condition is associated with SBF1 p.Asp1002= (c.3006C>T)?

SBF1 p.Asp1002= (c.3006C>T) is associated with Charcot-Marie-Tooth disease type 4B3 (ClinVar).

How is Charcot-Marie-Tooth disease type 4B3 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SBF1 p.Asp1002=

Q: How common is SBF1 p.Asp1002= (c.3006C>T) in the general population?

SBF1 p.Asp1002= (c.3006C>T) is common (popmax 6.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3006C>T · rs77064034 · VCV784995

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 6.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Charcot-Marie-Tooth disease type 4B3

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 0.49	GERP -4.2, phastCons 0.99
Overall
CADD	6.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.3% African / African-American · 4,724/75,042 alleles

Filtering AF 6.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.08%

Overall 0.338% 5,462/1,613,832 alleles · common exomes 2,722/1,461,506 · genomes 2,740/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.3%	16
Middle Eastern	0.455%	220
Remaining individualsnot grpmax-eligible	0.451%	222
Admixed American	0.387%	259
European (non-Finnish)	0.0158%	6,344
South Asian	0.0121%	8,280

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: SBF1
Protein: p.Asp1002=
Coding: c.3006C>T
MANE Select: NM_002972
dbSNP: rs77064034
Type: single nucleotide variant
Location: chr22:50460674 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72

Full SBF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 4B3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Charcot-Marie-Tooth disease type 4B3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

SBF1 c.3826+1G>A Pathogenic/Likely pathogenic ★★ same condition
SBF1 p.Met417Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
SBF1 c.4554+6C>T Uncertain significance ★★ same condition
SBF1 p.Ala1258Thr Uncertain significance ★★ ⚠ same condition
SBF1 p.Ala1836Gly Uncertain significance ★★ ⚠ same condition
SBF1 p.Ala1836Val Uncertain significance ★★ ⚠ same condition
SBF1 p.Ala913Thr Uncertain significance ★★ ⚠ same condition
SBF1 p.Arg1323Trp 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/sbf1-p-asp1002 (accessed [today's date]).

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