Is FUT4 p.Pro287Ser (c.859C>T) pathogenic?

FUT4 p.Pro287Ser (c.859C>T) is classified Uncertain significance in FUT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: ambiguous (0.3713); Ultra-rare (popmax 0.0329%, mid).

How common is FUT4 p.Pro287Ser (c.859C>T) in the general population?

FUT4 p.Pro287Ser (c.859C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about FUT4 p.Pro287Ser (c.859C>T)?

AlphaMissense predicts ambiguous (score 0.3713) — an in-silico prediction, not a clinical call.

FUT4 p.Pro287Ser

c.859C>T · VCV4260657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3713 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3713	ambiguous
REVEL	0.171	moderately benign-leaning
SaProt	LLR -11.77	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 7.3	GERP 1.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 866 bp · p 0.24 · regional, not allelic
Overall
CADD	24.3	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 0.0329% Middle Eastern · 2/6,074 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00355% 57/1,606,478 alleles · ultra-rare exomes 53/1,454,342 · genomes 4/152,136 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,037
Remaining individualsnot grpmax-eligible	0.00967%	10,338
European (non-Finnish)	0.00374%	26,739
Admixed American	0.00336%	29,734
African / African-American	0.00268%	37,346
East Asian	0.00224%	44,546

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: FUT4
Protein: p.Pro287Ser
Coding: c.859C>T
MANE Select: NM_002033
Type: single nucleotide variant
Location: chr11:94544992 (GRCh38)
Gene constraint: LOEUF 1.216 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 74.21

Full FUT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FUT4 p.Asp516Glu Likely benign ★★ same type
FUT4 p.Pro54= Benign ★★ same type
FUT4 p.Ala119Thr Uncertain significance ★ ⚠ same type
FUT4 p.Ala120Gly Uncertain significance ★ ⚠ same type
FUT4 p.Ala128Val Uncertain significance ★ ⚠ same type
FUT4 p.Ala14Gly Uncertain significance ★ ⚠ same type
FUT4 p.Ala14Ser Uncertain significance ★ ⚠ same type
FUT4 p.Ala157Pro Uncertain significance ★ ⚠ same type

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/fut4-p-pro287ser (accessed [today's date]).

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