Is FUCA1 p.Ala3Pro (c.7G>C) pathogenic?

FUCA1 p.Ala3Pro (c.7G>C) is classified Benign/Likely benign in FUCA1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0804); Low-frequency (popmax 4.89%, amr); Associated with fucosidosis.

What condition is associated with FUCA1 p.Ala3Pro (c.7G>C)?

FUCA1 p.Ala3Pro (c.7G>C) is associated with fucosidosis (ClinVar).

How common is FUCA1 p.Ala3Pro (c.7G>C) in the general population?

FUCA1 p.Ala3Pro (c.7G>C) is low-frequency (popmax 4.89%, amr) (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.Ala3Pro (c.7G>C)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

FUCA1 p.Ala3Pro

c.7G>C · rs61996282 · VCV296895

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.89%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

fucosidosis

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -6.46	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 -6.8	GERP -4.8
Regional constraint	o/e 0.96	unconstrained · MANE · 23 kb · p 0.31 · regional, not allelic
Overall
CADD	1.537	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.89% Admixed American · 2,532/51,738 alleles

Filtering AF 4.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.67%

Overall 0.963% 14,920/1,549,772 alleles · low-frequency exomes 13,485/1,397,502 · genomes 1,435/152,270 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	4.89%	20
South Asian	1.57%	64
Middle Eastern	1.03%	97
Remaining individualsnot grpmax-eligible	0.998%	100
European (non-Finnish)	0.881%	114
African / African-American	0.208%	480
Finnishnot grpmax-eligible	0.15%	666
Ashkenazi Jewishnot grpmax-eligible	0.126%	797
East Asian	0.0121%	8,282

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.Ala3Pro
Coding: c.7G>C
MANE Select: NM_000147
dbSNP: rs61996282
Type: single nucleotide variant
Location: chr1:23868280 (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.Ala3Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
FUCA1 p.Ala3Val Uncertain significance ★ ⚠ same residue
FUCA1 p.Ala3= Likely benign ★ same residue
FUCA1 p.Ala3fs Pathogenic/Likely pathogenic ★★ same residue
FUCA1 p.Ala3Ser 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

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-ala3pro (accessed [today's date]).

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