Is SBF2 p.Pro1430Ser (c.4288C>T) pathogenic?

SBF2 p.Pro1430Ser (c.4288C>T) is classified Uncertain significance in SBF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-21). AlphaMissense: ambiguous (0.3465); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with SBF2 p.Pro1430Ser (c.4288C>T)?

SBF2 p.Pro1430Ser (c.4288C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Pro1430Ser (c.4288C>T) in the general population?

SBF2 p.Pro1430Ser (c.4288C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about SBF2 p.Pro1430Ser (c.4288C>T)?

AlphaMissense predicts ambiguous (score 0.3465) — an in-silico prediction, not a clinical call.

SBF2 p.Pro1430Ser

c.4288C>T · rs1312716983 · VCV1347311

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3465 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3465	ambiguous
REVEL	0.912	moderately pathogenic-leaning
SaProt	LLR -8.68	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.23	gain · loss 0.16 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 514 kb · p 7.7e-06 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,910 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,952 alleles · very rare exomes 2/1,461,794 · genomes 1/152,158 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,910
European (non-Finnish)	0.000169%	590,002

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.Pro1430Ser
Coding: c.4288C>T
MANE Select: NM_030962
dbSNP: rs1312716983
Type: single nucleotide variant
Location: chr11:9808155 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 1430: the myotubularin phosphatase 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 4

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-pro1430ser (accessed [today's date]).

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