Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 10 submitters
gnomAD v4.1
Common
common (popmax 55.6%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
fructose-1,6-bisphosphatase deficiency
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP 0.91, phastCons 1 |
| Overall | ||
| CADD | 13.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
55.6%
East Asian · 24,938/44,852 alleles
Filtering AF
55%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 54.8%
Overall
33.5%
541,181/1,613,350 alleles · common
exomes 493,510/1,461,176 · genomes 47,671/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 55.6% | 2 |
| Finnishnot grpmax-eligible | 38.7% | 3 |
| South Asian | 36.9% | 3 |
| European (non-Finnish) | 33.7% | 3 |
| Remaining individualsnot grpmax-eligible | 32.3% | 3 |
| African / African-American | 26.8% | 4 |
| Amishnot grpmax-eligible | 24.2% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 22.5% | 4 |
| Middle Eastern | 22.4% | 4 |
| Admixed American | 20% | 5 |
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
- FBP1
- Protein
- p.Ala217=
- Coding
- c.651C>T
- MANE Select
- NM_000507
- dbSNP
- rs1042144
- Type
- single nucleotide variant
- Location
- chr9:94606869 (GRCh38)
- Gene constraint
- LOEUF 1.156 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 94.46 · 51 PDB
- Residue 217
- an α-helix
Disease context
fructose-1,6-bisphosphatase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Fructose-1,6-bisphosphatase deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
- Prevalence
- 1-9 / 1 000 000 (Italy)
Similar variants
- FBP1 p.Ala217Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
- FBP1 c.426+1G>A Pathogenic ★★ same condition
- FBP1 c.427-2A>G Likely pathogenic ★★ same condition
- FBP1 p.Arg158Trp Pathogenic ★★ same condition
- FBP1 p.Asp119Asn Pathogenic/Likely pathogenic ★★ same condition
- FBP1 p.Glu281Lys Pathogenic/Likely pathogenic ★★ same condition
- FBP1 p.Glu281Ter Pathogenic ★★ same condition
- FBP1 p.Gly164Ser Pathogenic/Likely pathogenic ★★ ⚠ 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/fbp1-p-ala217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown