Is FBP1 p.Pro235= (c.705A>G) pathogenic?

FBP1 p.Pro235= (c.705A>G) is classified Conflicting classifications of pathogenicity in FBP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2017-09-06). Very rare (popmax 0.00212%, nfe); Associated with fructose-1,6-bisphosphatase deficiency.

What condition is associated with FBP1 p.Pro235= (c.705A>G)?

FBP1 p.Pro235= (c.705A>G) is associated with fructose-1,6-bisphosphatase deficiency (ClinVar).

How common is FBP1 p.Pro235= (c.705A>G) in the general population?

FBP1 p.Pro235= (c.705A>G) is very rare (popmax 0.00212%, nfe) (gnomAD).

How is Fructose-1,6-bisphosphatase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

FBP1 p.Pro235=

c.705A>G · rs112446147 · VCV511580

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Conditions

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 -3.1	GERP -3.7
Overall
CADD	5.396	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,179,656 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00161% 26/1,613,372 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,186
African / African-American	0.00133%	74,910

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.Pro235=
Coding: c.705A>G
MANE Select: NM_000507
dbSNP: rs112446147
Type: single nucleotide variant
Location: chr9:94606815 (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 235: a β-strand

Full FBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

fructose-1,6-bisphosphatase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Fructose-1,6-bisphosphatase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Italy)

Similar variants

FBP1 p.Pro235Leu Uncertain significance ★★ ⚠ same residue
FBP1 p.Pro235Arg Uncertain significance ★ ⚠ same residue
FBP1 p.Pro235fs Pathogenic/Likely pathogenic ★★ same residue
FBP1 p.Pro235Gln Uncertain significance ★ ⚠ 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

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-pro235 (accessed [today's date]).

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