Is B4GALNT1 p.Gly467Glu (c.1400G>A) pathogenic?

B4GALNT1 p.Gly467Glu (c.1400G>A) is classified Uncertain significance in B4GALNT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-14). AlphaMissense: likely pathogenic (0.9842); Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia 26.

What condition is associated with B4GALNT1 p.Gly467Glu (c.1400G>A)?

B4GALNT1 p.Gly467Glu (c.1400G>A) is associated with hereditary spastic paraplegia 26 (ClinVar).

How common is B4GALNT1 p.Gly467Glu (c.1400G>A) in the general population?

B4GALNT1 p.Gly467Glu (c.1400G>A) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal recessive spastic paraplegia type 26 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about B4GALNT1 p.Gly467Glu (c.1400G>A)?

AlphaMissense predicts likely pathogenic (score 0.9842) — an in-silico prediction, not a clinical call.

B4GALNT1 p.Gly467Glu

c.1400G>A · rs1555185818 · VCV451967

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9842 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary spastic paraplegia 26

Computational evidence

Protein change
AlphaMissense	0.9842	likely pathogenic · top 5% in B4GALNT1
REVEL	0.666	pathogenic-leaning
SaProt	LLR -14.69	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,385 bp · p 0.015 · regional, not allelic
Overall
CADD	28.7	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: B4GALNT1
Protein: p.Gly467Glu
Coding: c.1400G>A
MANE Select: NM_001478
dbSNP: rs1555185818
Type: single nucleotide variant
Location: chr12:57626946 (GRCh38)
Gene constraint: LOEUF 1.114 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.79 · 3 PDB
Residue 467: a disulfide bond; a turn

Full B4GALNT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 26 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 26 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

Similar variants

B4GALNT1 c.532-2A>G Pathogenic/Likely pathogenic ★★ same condition
B4GALNT1 p.Ala441Glu Likely pathogenic ★★ same condition
B4GALNT1 p.Arg228Ter Pathogenic ★★ same condition
B4GALNT1 p.Arg505Cys Pathogenic/Likely pathogenic ★★ same condition
B4GALNT1 p.Arg505His Pathogenic/Likely pathogenic ★★ same condition
B4GALNT1 p.Ala363Gly Uncertain significance ★★ ⚠ same condition
B4GALNT1 p.Lys350Glu Uncertain significance ★★ ⚠ same condition
B4GALNT1 p.Met515Ile 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/b4galnt1-p-gly467glu (accessed [today's date]).

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