Is FUCA1 p.Pro13Ser (c.37C>T) pathogenic?

FUCA1 p.Pro13Ser (c.37C>T) is classified Uncertain significance in FUCA1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-09). AlphaMissense: likely benign (0.0932); Rare (popmax 0.231%, mid); Associated with fucosidosis.

What condition is associated with FUCA1 p.Pro13Ser (c.37C>T)?

FUCA1 p.Pro13Ser (c.37C>T) is associated with fucosidosis (ClinVar).

How common is FUCA1 p.Pro13Ser (c.37C>T) in the general population?

FUCA1 p.Pro13Ser (c.37C>T) is rare (popmax 0.231%, mid) (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.Pro13Ser (c.37C>T)?

AlphaMissense predicts likely benign (score 0.0932) — an in-silico prediction, not a clinical call.

FUCA1 p.Pro13Ser

c.37C>T · rs569701574 · VCV1476068

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0932 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.231%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

fucosidosis

Computational evidence

Protein change
AlphaMissense	0.0932	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.1	GERP -4.2
Regional constraint	o/e 0.96	unconstrained · MANE · 23 kb · p 0.31 · regional, not allelic
Overall
CADD	0.046	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 0.231% Middle Eastern · 13/5,632 alleles

Filtering AF 0.136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.00687% 107/1,558,560 alleles · rare exomes 95/1,406,250 · genomes 12/152,310 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.231%	433
Admixed American	0.0344%	2,905
Remaining individualsnot grpmax-eligible	0.0199%	5,036
European (non-Finnish)	0.00529%	18,905
East Asian	0.00481%	20,791
African / African-American	0.00136%	73,644

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.Pro13Ser
Coding: c.37C>T
MANE Select: NM_000147
dbSNP: rs569701574
Type: single nucleotide variant
Location: chr1:23868250 (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.Pro13= Likely benign ★ same residue
FUCA1 p.Pro13Ala Likely benign ★ 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

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-pro13ser (accessed [today's date]).

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