Is FUT8 p.Arg2Trp (c.4C>T) pathogenic?

FUT8 p.Arg2Trp (c.4C>T) is classified Uncertain significance in FUT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). AlphaMissense: likely pathogenic (0.6499); Ultra-rare (popmax 0.0242%, sas); Associated with Inborn genetic diseases.

What condition is associated with FUT8 p.Arg2Trp (c.4C>T)?

FUT8 p.Arg2Trp (c.4C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FUT8 p.Arg2Trp (c.4C>T) in the general population?

FUT8 p.Arg2Trp (c.4C>T) is ultra-rare (popmax 0.0242%, sas) (gnomAD).

What do computational predictors say about FUT8 p.Arg2Trp (c.4C>T)?

AlphaMissense predicts likely pathogenic (score 0.6499) — an in-silico prediction, not a clinical call.

FUT8 p.Arg2Trp

c.4C>T · VCV3280225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6499 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6499	likely pathogenic
REVEL	0.304	indeterminate
SaProt	LLR -9.66	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 181 kb · p 2.4e-09 · regional, not allelic
Overall
CADD	34.0	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 0.0242% South Asian · 22/91,016 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00248% 40/1,612,700 alleles · ultra-rare exomes 36/1,460,640 · genomes 4/152,060 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0242%	4,137
African / African-American	0.00668%	14,962
Remaining individualsnot grpmax-eligible	0.0016%	62,404
Finnishnot grpmax-eligible	0.00156%	64,008
European (non-Finnish)	0.000933%	107,208

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.Arg2Trp
Coding: c.4C>T
MANE Select: NM_001371533
Type: single nucleotide variant
Location: chr14:65561567 (GRCh38)
Gene constraint: LOEUF 0.667 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.03 · 14 PDB

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.Arg2= Likely benign ★ 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-arg2trp (accessed [today's date]).

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