Is B4GALNT1 p.Phe359= (c.1077C>T) pathogenic?

B4GALNT1 p.Phe359= (c.1077C>T) is classified Likely benign in B4GALNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-07-06). Ultra-rare (popmax 0.0178%, eas); Associated with Spastic paraplegia.

What condition is associated with B4GALNT1 p.Phe359= (c.1077C>T)?

B4GALNT1 p.Phe359= (c.1077C>T) is associated with Spastic paraplegia (ClinVar).

How common is B4GALNT1 p.Phe359= (c.1077C>T) in the general population?

B4GALNT1 p.Phe359= (c.1077C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

B4GALNT1 p.Phe359=

c.1077C>T · rs541794502 · VCV413849

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

Spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.084	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.02	GERP -4.7
Overall
CADD	6.273	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,892 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000681% 11/1,614,260 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,612
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.000169%	590,023

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: B4GALNT1
Protein: p.Phe359=
Coding: c.1077C>T
MANE Select: NM_001478
dbSNP: rs541794502
Type: single nucleotide variant
Location: chr12:57628188 (GRCh38)
Gene constraint: LOEUF 1.114 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.79 · 3 PDB
Residue 359: a β-strand

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

Disease context

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

Similar variants

B4GALNT1 p.Phe359Leu Uncertain significance ★ ⚠ same residue
B4GALNT1 c.383+1G>A Likely pathogenic ★★ same condition
B4GALNT1 c.490+1G>A Pathogenic/Likely pathogenic ★★ same condition
B4GALNT1 c.532-2A>G Pathogenic/Likely pathogenic ★★ same condition
B4GALNT1 p.Ala393Val Uncertain significance ★★ ⚠ same condition
B4GALNT1 p.Ala7Thr Uncertain significance ★★ ⚠ same condition
B4GALNT1 p.Arg300His Uncertain significance ★★ ⚠ same condition
B4GALNT1 p.Arg397Trp 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-phe359 (accessed [today's date]).

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