Is B4GALNT1 p.Pro331Ser (c.991C>T) pathogenic?

B4GALNT1 p.Pro331Ser (c.991C>T) is classified Uncertain significance in B4GALNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-12). AlphaMissense: likely pathogenic (0.8407); Absent from gnomAD v4.1; Associated with Spastic paraplegia.

What condition is associated with B4GALNT1 p.Pro331Ser (c.991C>T)?

B4GALNT1 p.Pro331Ser (c.991C>T) is associated with Spastic paraplegia (ClinVar).

How common is B4GALNT1 p.Pro331Ser (c.991C>T) in the general population?

B4GALNT1 p.Pro331Ser (c.991C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about B4GALNT1 p.Pro331Ser (c.991C>T)?

AlphaMissense predicts likely pathogenic (score 0.8407) — an in-silico prediction, not a clinical call.

B4GALNT1 p.Pro331Ser

c.991C>T · rs2540657028 · VCV1993333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8407 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Spastic paraplegia

Computational evidence

Protein change
AlphaMissense	0.8407	likely pathogenic
REVEL	0.756	pathogenic-leaning
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,385 bp · p 0.015 · regional, not allelic
Overall
CADD	31.0	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

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.Pro331Ser
Coding: c.991C>T
MANE Select: NM_001478
dbSNP: rs2540657028
Type: single nucleotide variant
Location: chr12:57628724 (GRCh38)
Gene constraint: LOEUF 1.114 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.79 · 3 PDB

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 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
B4GALNT1 p.Asp511Glu 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-pro331ser (accessed [today's date]).

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