Is FUT8 p.Pro378Arg (c.1133C>G) pathogenic?

FUT8 p.Pro378Arg (c.1133C>G) is classified Uncertain significance in FUT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: ambiguous (0.4161); Very rare (popmax 0.00268%, afr); Associated with Inborn genetic diseases.

What condition is associated with FUT8 p.Pro378Arg (c.1133C>G)?

FUT8 p.Pro378Arg (c.1133C>G) is associated with Inborn genetic diseases (ClinVar).

How common is FUT8 p.Pro378Arg (c.1133C>G) in the general population?

FUT8 p.Pro378Arg (c.1133C>G) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about FUT8 p.Pro378Arg (c.1133C>G)?

AlphaMissense predicts ambiguous (score 0.4161) — an in-silico prediction, not a clinical call.

FUT8 p.Pro378Arg

c.1133C>G · VCV4620430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4161 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4161	ambiguous
REVEL	0.174	moderately benign-leaning
SaProt	LLR -11.06	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 181 kb · p 2.4e-09 · regional, not allelic
Overall
CADD	24.1	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 0.00268% African / African-American · 2/74,716 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,609,312 alleles · very rare exomes 0/1,457,168 · genomes 2/152,144 · 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: FUT8
Protein: p.Pro378Arg
Coding: c.1133C>G
MANE Select: NM_001371533
Type: single nucleotide variant
Location: chr14:65724197 (GRCh38)
Gene constraint: LOEUF 0.667 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.03 · 14 PDB
Residue 378: a UniProt-annotated variant site (in cdgf1; drastic decrease of protein level in patient's fibroblasts and complete loss of total core fucosylated n-glycans in serum and fibroblasts compared to controls); a UniProt-annotated variant site (in cdgf1; uncertain significance); a UniProt-annotated variant site (in cdgf1; complete loss of total core fucosylated n-glycans in patient's serum and fibroblasts compared to controls); the gt23 domain

Full FUT8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FUT8 p.Pro378Leu Uncertain significance ★ ⚠ same residue
FUT8 p.Arg239Ter Pathogenic ★★ same condition
FUT8 p.Ala518Thr Uncertain significance ★★ ⚠ same condition
FUT8 p.Arg395Cys Uncertain significance ★★ ⚠ same condition
FUT8 p.Gly107Asp Uncertain significance ★★ ⚠ same condition
FUT8 p.Gly437Val Uncertain significance ★★ ⚠ same condition
FUT8 p.Ile163Val Uncertain significance ★★ ⚠ same condition
FUT8 p.Ile454Val Uncertain significance ★★ ⚠ 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/fut8-p-pro378arg (accessed [today's date]).

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