Is FUCA1 p.Pro99fs (c.293dup) pathogenic?

FUCA1 p.Pro99fs (c.293dup) is classified Pathogenic in FUCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-01). No gnomAD frequency available for this variant; Associated with fucosidosis.

What condition is associated with FUCA1 p.Pro99fs (c.293dup)?

FUCA1 p.Pro99fs (c.293dup) is associated with fucosidosis (ClinVar).

How common is FUCA1 p.Pro99fs (c.293dup) in the general population?

FUCA1 p.Pro99fs (c.293dup) is no gnomAD frequency available for this variant (gnomAD).

How is Fucosidosis inherited?

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

FUCA1 p.Pro99fs

c.293dup · rs2521759907 · VCV2757124

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

fucosidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.2	GERP 0.27

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FUCA1
Protein: p.Pro99fs
Coding: c.293dup
MANE Select: NM_000147
dbSNP: rs2521759907
Type: Duplication
Location: chr1:23867993 (GRCh38)
Gene constraint: LOEUF 1.162 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.60 · 2 PDB

Full FUCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

fucosidosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Fucosidosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

FUCA1 p.Pro99= Likely benign ★ same residue
FUCA1 p.Leu20_Phe21insLeuLeu Uncertain significance ★★ same condition
FUCA1 c.3_4insAGGGGTAGCGATG Likely pathogenic ★ same condition
FUCA1 p.Glu187fs Likely pathogenic ★ same condition
FUCA1 p.Leu185fs Likely pathogenic ★ same condition
FUCA1 p.Lys57fs Pathogenic ★ same condition
FUCA1 p.Met6fs Pathogenic ★ same condition
FUCA1 p.Tyr179fs 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/fuca1-p-pro99fs (accessed [today's date]).

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