Is FUT8 p.Pro358Ala (c.1072C>G) pathogenic?

FUT8 p.Pro358Ala (c.1072C>G) is classified Uncertain significance in FUT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-13). AlphaMissense: likely pathogenic (0.7896); Absent from gnomAD v4.1.

How common is FUT8 p.Pro358Ala (c.1072C>G) in the general population?

FUT8 p.Pro358Ala (c.1072C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FUT8 p.Pro358Ala (c.1072C>G)?

AlphaMissense predicts likely pathogenic (score 0.7896) — an in-silico prediction, not a clinical call.

FUT8 p.Pro358Ala

c.1072C>G · rs2503436687 · VCV2852546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7896 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7896	likely pathogenic
REVEL	0.596	indeterminate
SaProt	LLR -15.22	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 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	26.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FUT8
Protein: p.Pro358Ala
Coding: c.1072C>G
MANE Select: NM_001371533
dbSNP: rs2503436687
Type: single nucleotide variant
Location: chr14:65722011 (GRCh38)
Gene constraint: LOEUF 0.667 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.03 · 14 PDB
Residue 358: 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; a β-strand

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

Similar variants

FUT8 p.Arg239Ter Pathogenic ★★ same type
FUT8 p.Ala518Thr Uncertain significance ★★ ⚠ same type
FUT8 p.Arg395Cys Uncertain significance ★★ ⚠ same type
FUT8 p.Arg559Ter Uncertain significance ★★ same type
FUT8 p.Gly107Asp Uncertain significance ★★ ⚠ same type
FUT8 p.Gly437Val Uncertain significance ★★ ⚠ same type
FUT8 p.Ile163Val Uncertain significance ★★ ⚠ same type
FUT8 p.Ile454Val 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/fut8-p-pro358ala (accessed [today's date]).

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