Is FUCA1 p.Pro10Arg (c.29C>G) pathogenic?

FUCA1 p.Pro10Arg (c.29C>G) is classified Benign in FUCA1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0668); Common (popmax 17.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with fucosidosis.

What condition is associated with FUCA1 p.Pro10Arg (c.29C>G)?

FUCA1 p.Pro10Arg (c.29C>G) is associated with fucosidosis (ClinVar).

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.Pro10Arg (c.29C>G)?

AlphaMissense predicts likely benign (score 0.0668) — an in-silico prediction, not a clinical call.

FUCA1 p.Pro10Arg

Q: How common is FUCA1 p.Pro10Arg (c.29C>G) in the general population?

FUCA1 p.Pro10Arg (c.29C>G) is common (popmax 17.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.29C>G · rs2070956 · VCV193053

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0668 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 17.9%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

fucosidosis

Computational evidence

Protein change
AlphaMissense	0.0668	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -6.41	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 -5.3	GERP -5.2
Regional constraint	o/e 0.96	unconstrained · MANE · 23 kb · p 0.31 · regional, not allelic
Overall
CADD	8.358	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 17.9% East Asian · 7,443/41,598 alleles

Filtering AF 17.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.4%

Overall 10.1% 157,541/1,556,742 alleles · common exomes 141,225/1,404,520 · genomes 16,316/152,222 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	17.9%	6
Ashkenazi Jewishnot grpmax-eligible	13.4%	7
South Asian	12.5%	8
Admixed American	12%	8
African / African-American	11.8%	9
Remaining individualsnot grpmax-eligible	10.8%	9
European (non-Finnish)	9.67%	10
Middle Eastern	6.74%	15
Finnishnot grpmax-eligible	4.01%	25
Amishnot grpmax-eligible	3.3%	30

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.Pro10Arg
Coding: c.29C>G
MANE Select: NM_000147
dbSNP: rs2070956
Type: single nucleotide variant
Location: chr1:23868258 (GRCh38)
Gene constraint: LOEUF 1.162 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.60 · 2 PDB
Residue 10: a UniProt-annotated variant site (in)

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.Pro10= Likely benign ★ same residue
FUCA1 p.Pro10Leu 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-pro10arg (accessed [today's date]).

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