Is FBP1 p.Asp323= (c.969C>T) pathogenic?

FBP1 p.Asp323= (c.969C>T) is classified Likely benign in FBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-28). Very rare (popmax 0.005%, amr); Associated with fructose-1,6-bisphosphatase deficiency.

What condition is associated with FBP1 p.Asp323= (c.969C>T)?

FBP1 p.Asp323= (c.969C>T) is associated with fructose-1,6-bisphosphatase deficiency (ClinVar).

How common is FBP1 p.Asp323= (c.969C>T) in the general population?

FBP1 p.Asp323= (c.969C>T) is very rare (popmax 0.005%, amr) (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.Asp323=

c.969C>T · rs372074976 · VCV2725139

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 -3.5	GERP -3.7
Overall
CADD	0.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,008 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00242% 39/1,614,072 alleles · very rare exomes 39/1,461,828 · genomes 0/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
European (non-Finnish)	0.00297%	33,714
African / African-American	0.00133%	75,030

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.Asp323=
Coding: c.969C>T
MANE Select: NM_000507
dbSNP: rs372074976
Type: single nucleotide variant
Location: chr9:94603429 (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 323: an α-helix

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.Asp323fs 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-asp323 (accessed [today's date]).

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