Is SBF2 p.Val1244Ala (c.3731T>C) pathogenic?

SBF2 p.Val1244Ala (c.3731T>C) is classified Uncertain significance in SBF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-18). AlphaMissense: likely benign (0.1134); Ultra-rare (popmax 0.011%, sas); Associated with Inborn genetic diseases.

What condition is associated with SBF2 p.Val1244Ala (c.3731T>C)?

SBF2 p.Val1244Ala (c.3731T>C) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is SBF2 p.Val1244Ala (c.3731T>C) in the general population?

SBF2 p.Val1244Ala (c.3731T>C) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about SBF2 p.Val1244Ala (c.3731T>C)?

AlphaMissense predicts likely benign (score 0.1134) — an in-silico prediction, not a clinical call.

SBF2 p.Val1244Ala

c.3731T>C · rs757063919 · VCV1485075

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1134 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1134	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -6.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.20	acceptor loss, 8 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 514 kb · p 7.7e-06 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,060 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.000868% 14/1,613,210 alleles · ultra-rare exomes 13/1,461,008 · genomes 1/152,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,106
Admixed American	0.00333%	30,003
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	8.48e-05%	1,179,281

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.Val1244Ala
Coding: c.3731T>C
MANE Select: NM_030962
dbSNP: rs757063919
Type: single nucleotide variant
Location: chr11:9829418 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 1244: 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-val1244ala (accessed [today's date]).

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