Is FUCA1 p.Arg30Pro (c.89G>C) pathogenic?

FUCA1 p.Arg30Pro (c.89G>C) is classified Uncertain significance in FUCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). AlphaMissense: likely benign (0.0777); Very rare (popmax 6.26e-05%); Associated with fucosidosis.

What condition is associated with FUCA1 p.Arg30Pro (c.89G>C)?

FUCA1 p.Arg30Pro (c.89G>C) is associated with fucosidosis (ClinVar).

How common is FUCA1 p.Arg30Pro (c.89G>C) in the general population?

FUCA1 p.Arg30Pro (c.89G>C) is very rare (popmax 6.26e-05%) (gnomAD).

How is Fucosidosis inherited?

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

What do computational predictors say about FUCA1 p.Arg30Pro (c.89G>C)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

FUCA1 p.Arg30Pro

c.89G>C · rs1639666007 · VCV2047900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.26e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

fucosidosis

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -6.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.96	GERP -2
Regional constraint	o/e 0.96	unconstrained · MANE · 23 kb · p 0.31 · regional, not allelic
Overall
CADD	11.65	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.26e-05%

Overall 6.26e-05% 1/1,598,140 alleles · very rare exomes 1/1,445,896 · genomes 0/152,244 · joint denominator

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.Arg30Pro
Coding: c.89G>C
MANE Select: NM_000147
dbSNP: rs1639666007
Type: single nucleotide variant
Location: chr1:23868198 (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.Arg30Trp Uncertain significance ★★ ⚠ same residue
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

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-arg30pro (accessed [today's date]).

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