Is B4GALNT1 p.Pro404Ser (c.1210C>T) pathogenic?

B4GALNT1 p.Pro404Ser (c.1210C>T) is classified Uncertain significance in B4GALNT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-16). AlphaMissense: likely benign (0.0722); Very rare (popmax 0.0017%, amr); Associated with Spastic paraplegia.

What condition is associated with B4GALNT1 p.Pro404Ser (c.1210C>T)?

B4GALNT1 p.Pro404Ser (c.1210C>T) is associated with Spastic paraplegia (ClinVar).

How common is B4GALNT1 p.Pro404Ser (c.1210C>T) in the general population?

B4GALNT1 p.Pro404Ser (c.1210C>T) is very rare (popmax 0.0017%, amr) (gnomAD).

What do computational predictors say about B4GALNT1 p.Pro404Ser (c.1210C>T)?

AlphaMissense predicts likely benign (score 0.0722) — an in-silico prediction, not a clinical call.

B4GALNT1 p.Pro404Ser

c.1210C>T · rs756953267 · VCV2415745

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0722 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Spastic paraplegia

Computational evidence

Protein change
AlphaMissense	0.0722	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -8.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.53, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,385 bp · p 0.015 · regional, not allelic
Overall
CADD	19.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0017% Admixed American · 1/58,822 alleles

Filtering AF 0.000361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000262%

Overall 0.000692% 10/1,445,812 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0017%	58,822
European (non-Finnish)	0.000768%	130,187

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.Pro404Ser
Coding: c.1210C>T
MANE Select: NM_001478
dbSNP: rs756953267
Type: single nucleotide variant
Location: chr12:57627792 (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 p.Pro404= Likely benign ★ 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-pro404ser (accessed [today's date]).

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