Is FUCA1 p.Ile347= (c.1041T>C) pathogenic?

FUCA1 p.Ile347= (c.1041T>C) is classified Likely benign in FUCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). Ultra-rare (popmax 0.0164%, mid); Associated with fucosidosis.

What condition is associated with FUCA1 p.Ile347= (c.1041T>C)?

FUCA1 p.Ile347= (c.1041T>C) is associated with fucosidosis (ClinVar).

How common is FUCA1 p.Ile347= (c.1041T>C) in the general population?

FUCA1 p.Ile347= (c.1041T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Fucosidosis inherited?

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

FUCA1 p.Ile347=

c.1041T>C · rs1230687658 · VCV2915985

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

fucosidosis

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 -2.2	GERP -4.9
Overall
CADD	1.463	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000805% 13/1,614,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.00667%	15,002
Remaining individualsnot grpmax-eligible	0.0048%	20,828
European (non-Finnish)	0.000424%	236,000

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: FUCA1
Protein: p.Ile347=
Coding: c.1041T>C
MANE Select: NM_000147
dbSNP: rs1230687658
Type: single nucleotide variant
Location: chr1:23848768 (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 c.768+1G>A Pathogenic/Likely pathogenic ★★ same condition
FUCA1 c.768+1G>T Likely pathogenic ★★ same condition
FUCA1 p.Arg264Ter Pathogenic ★★ same condition
FUCA1 p.Gln427Ter Pathogenic ★★ same condition
FUCA1 p.Gln82Ter Pathogenic ★★ same condition
FUCA1 p.Glu318Ter Pathogenic/Likely pathogenic ★★ same condition
FUCA1 p.Glu353Ter Pathogenic ★★ same condition
FUCA1 p.Glu380Ter 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-ile347 (accessed [today's date]).

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