Is SBF2 p.Val355Met (c.1063G>A) pathogenic?

SBF2 p.Val355Met (c.1063G>A) is classified Uncertain significance in SBF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-11). AlphaMissense: ambiguous (0.4651); Very rare (popmax 8.52e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SBF2 p.Val355Met (c.1063G>A)?

SBF2 p.Val355Met (c.1063G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SBF2 p.Val355Met (c.1063G>A) in the general population?

SBF2 p.Val355Met (c.1063G>A) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

What do computational predictors say about SBF2 p.Val355Met (c.1063G>A)?

AlphaMissense predicts ambiguous (score 0.4651) — an in-silico prediction, not a clinical call.

SBF2 p.Val355Met

c.1063G>A · rs1947514137 · VCV1781067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4651	ambiguous
REVEL	0.311	indeterminate
SaProt	LLR -10.82	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 514 kb · p 7.7e-06 · regional, not allelic
Overall
CADD	23.9	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 8.52e-05% European (non-Finnish) · 1/1,174,390 alleles

Overall 6.23e-05% 1/1,605,412 alleles · very rare exomes 1/1,453,186 · genomes 0/152,226 · 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: SBF2
Protein: p.Val355Met
Coding: c.1063G>A
MANE Select: NM_030962
dbSNP: rs1947514137
Type: single nucleotide variant
Location: chr11:9993094 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.74
Residue 355: the ddenn 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

Similar variants

SBF2 p.Val355= Likely benign ★ same residue
SBF2 p.Arg77Ter Pathogenic ★★ same condition
SBF2 c.1601-3T>G Uncertain significance ★★ same condition
SBF2 c.4258-4C>G Uncertain significance ★★ same condition
SBF2 p.Ala117Gly Uncertain significance ★★ ⚠ same condition
SBF2 p.Arg1173His Uncertain significance ★★ ⚠ same condition
SBF2 p.Arg1176Gln Uncertain significance ★★ ⚠ same condition
SBF2 p.Arg1312Gln 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-val355met (accessed [today's date]).

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