Is SBF1 p.Ser1237Asn (c.3710G>A) pathogenic?

SBF1 p.Ser1237Asn (c.3710G>A) is classified Uncertain significance in SBF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-08). AlphaMissense: likely benign (0.2509); Very rare (popmax 0.000339%, nfe).

How common is SBF1 p.Ser1237Asn (c.3710G>A) in the general population?

SBF1 p.Ser1237Asn (c.3710G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about SBF1 p.Ser1237Asn (c.3710G>A)?

AlphaMissense predicts likely benign (score 0.2509) — an in-silico prediction, not a clinical call.

SBF1 p.Ser1237Asn

c.3710G>A · rs2521902055 · VCV2063391

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2509 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2509	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -8.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2.3, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.67 · regional, not allelic
Overall
CADD	23.9	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S1238N vs ClinVar S1237N) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,404 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,612,480 alleles · very rare exomes 4/1,460,128 · genomes 0/152,352 · joint denominator

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.Ser1237Asn
Coding: c.3710G>A
MANE Select: NM_002972
dbSNP: rs2521902055
Type: single nucleotide variant
Location: chr22:50459371 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 1238 UniProt numbering: the myotubularin phosphatase domain

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

Similar variants

SBF1 p.Ser1237= Likely benign ★ same residue
SBF1 c.3826+1G>A Pathogenic/Likely pathogenic ★★ same type
SBF1 p.Met417Val Pathogenic/Likely pathogenic ★★ ⚠ same type
SBF1 c.1431+6A>T Uncertain significance ★★ same type
SBF1 c.1636+4C>T Uncertain significance ★★ same type
SBF1 c.1899+3G>A Uncertain significance ★★ same type
SBF1 c.2643+6C>T Uncertain significance ★★ same type
SBF1 c.279+3C>T Uncertain significance ★★ same type

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-ser1237asn (accessed [today's date]).

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