Is SBF2 p.Pro339= (c.1017T>C) pathogenic?

SBF2 p.Pro339= (c.1017T>C) is classified Likely benign in SBF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). Very rare (popmax 0.00595%, nfe); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with SBF2 p.Pro339= (c.1017T>C)?

SBF2 p.Pro339= (c.1017T>C) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Pro339= (c.1017T>C) in the general population?

SBF2 p.Pro339= (c.1017T>C) is very rare (popmax 0.00595%, nfe) (gnomAD).

SBF2 p.Pro339=

c.1017T>C · rs374673632 · VCV2137779

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00595%, nfe)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP 0.11, phastCons 1
Overall
CADD	11.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00595% European (non-Finnish) · 50/839,714 alleles

Filtering AF 0.00458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00413%

Overall 0.00411% 51/1,241,360 alleles · very rare exomes 49/1,089,160 · genomes 2/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00595%	16,794
Remaining individualsnot grpmax-eligible	0.00199%	50,264

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.Pro339=
Coding: c.1017T>C
MANE Select: NM_030962
dbSNP: rs374673632
Type: single nucleotide variant
Location: chr11:9993957 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 339: the ddenn 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.Pro339Leu Uncertain significance ★ ⚠ same residue
SBF2 p.Pro339Ala 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

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-pro339 (accessed [today's date]).

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