Is B4GALT1 p.Pro87Ser (c.259C>T) pathogenic?

B4GALT1 p.Pro87Ser (c.259C>T) is classified Conflicting classifications of pathogenicity in B4GALT1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0649); Rare (popmax 0.596%, afr); Associated with B4GALT1-congenital disorder of glycosylation.

What condition is associated with B4GALT1 p.Pro87Ser (c.259C>T)?

B4GALT1 p.Pro87Ser (c.259C>T) is associated with B4GALT1-congenital disorder of glycosylation (ClinVar).

How common is B4GALT1 p.Pro87Ser (c.259C>T) in the general population?

B4GALT1 p.Pro87Ser (c.259C>T) is rare (popmax 0.596%, afr) (gnomAD).

How is B4GALT1-CDG inherited?

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

What do computational predictors say about B4GALT1 p.Pro87Ser (c.259C>T)?

AlphaMissense predicts likely benign (score 0.0649) — an in-silico prediction, not a clinical call.

B4GALT1 p.Pro87Ser

c.259C>T · rs149181384 · VCV719722

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0649 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.596%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

B4GALT1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0649	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.42	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 2.4	GERP 0.43, phastCons 0.97
Regional constraint	o/e 0.88	unconstrained · MANE · 51 kb · p 0.019 · regional, not allelic
Overall
CADD	18.05	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

Grpmax group 0.596% African / African-American · 445/74,602 alleles

Filtering AF 0.551% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.533%

Overall 0.0314% 495/1,576,632 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.596%	168
Remaining individualsnot grpmax-eligible	0.0407%	2,455
Middle Eastern	0.035%	2,856
Admixed American	0.0253%	3,947
South Asian	0.00113%	88,482
European (non-Finnish)	0.000685%	146,040

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: B4GALT1
Protein: p.Pro87Ser
Coding: c.259C>T
MANE Select: NM_001497
dbSNP: rs149181384
Type: single nucleotide variant
Location: chr9:33166911 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI 0.02 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.23 · 19 PDB
Residue 87: the 'disordered' region

Full B4GALT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

B4GALT1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For B4GALT1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

B4GALT1 p.Gly395Arg Uncertain significance ★★ ⚠ same condition
B4GALT1 p.Pro131Leu Uncertain significance ★★ ⚠ same condition
B4GALT1 p.Tyr239Cys Uncertain significance ★★ ⚠ same condition
B4GALT1 p.Val271Ile Uncertain significance ★★ ⚠ same condition
B4GALT1 c.648+102C>T Benign ★★ same condition
B4GALT1 p.Glu350= Benign/Likely benign ★★ same condition
B4GALT1 p.His199= Benign ★★ same condition
B4GALT1 p.Arg21Trp 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/b4galt1-p-pro87ser (accessed [today's date]).

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