Is FUT8 p.Ser7Phe (c.20C>T) pathogenic?

FUT8 p.Ser7Phe (c.20C>T) is classified Uncertain significance in FUT8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-07). AlphaMissense: likely pathogenic (0.6641); Ultra-rare (popmax 0.0215%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FUT8 p.Ser7Phe (c.20C>T)?

FUT8 p.Ser7Phe (c.20C>T) is associated with Inborn genetic diseases, congenital disorder of glycosylation with defective fucosylation 1 (ClinVar).

How common is FUT8 p.Ser7Phe (c.20C>T) in the general population?

FUT8 p.Ser7Phe (c.20C>T) is ultra-rare (popmax 0.0215%, nfe) (gnomAD).

What do computational predictors say about FUT8 p.Ser7Phe (c.20C>T)?

AlphaMissense predicts likely pathogenic (score 0.6641) — an in-silico prediction, not a clinical call.

FUT8 p.Ser7Phe

c.20C>T · VCV3280223

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6641 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0215%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6641	likely pathogenic
REVEL	0.406	indeterminate
SaProt	LLR -7.49	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 181 kb · p 2.4e-09 · regional, not allelic
Overall
CADD	32.0	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 0.0215% European (non-Finnish) · 254/1,179,516 alleles

Filtering AF 0.0193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.0165% 266/1,613,260 alleles · ultra-rare exomes 242/1,461,178 · genomes 24/152,082 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0215%	4,644
Remaining individualsnot grpmax-eligible	0.00801%	12,489
Finnishnot grpmax-eligible	0.00469%	21,339
East Asian	0.00446%	22,441
African / African-American	0.00267%	37,427

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.Ser7Phe
Coding: c.20C>T
MANE Select: NM_001371533
Type: single nucleotide variant
Location: chr14:65561583 (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

Also linked: congenital disorder of glycosylation with defective fucosylation 1

Similar variants

FUT8 p.Ser7= 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.Arg559Ter 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

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-ser7phe (accessed [today's date]).

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