Is FUCA1 p.Ala71Val (c.212C>T) pathogenic?

FUCA1 p.Ala71Val (c.212C>T) is classified Uncertain significance in FUCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-08). AlphaMissense: likely pathogenic (0.714); Very rare (popmax 0.00501%, amr); Associated with fucosidosis.

What condition is associated with FUCA1 p.Ala71Val (c.212C>T)?

FUCA1 p.Ala71Val (c.212C>T) is associated with fucosidosis (ClinVar).

How common is FUCA1 p.Ala71Val (c.212C>T) in the general population?

FUCA1 p.Ala71Val (c.212C>T) is very rare (popmax 0.00501%, 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.Ala71Val (c.212C>T)?

AlphaMissense predicts likely pathogenic (score 0.714) — an in-silico prediction, not a clinical call.

FUCA1 p.Ala71Val

c.212C>T · rs1224396509 · VCV1440424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.714 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

fucosidosis

Computational evidence

Protein change
AlphaMissense	0.714	likely pathogenic
REVEL	0.477	indeterminate
SaProt	LLR -11.96	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 23 kb · p 0.31 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00501% Admixed American · 3/59,868 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000186% 3/1,611,720 alleles · very rare exomes 3/1,459,408 · genomes 0/152,312 · 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.Ala71Val
Coding: c.212C>T
MANE Select: NM_000147
dbSNP: rs1224396509
Type: single nucleotide variant
Location: chr1:23868075 (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-ala71val (accessed [today's date]).

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