Is B4GALT1 p.Met366Val (c.1096A>G) pathogenic?

B4GALT1 p.Met366Val (c.1096A>G) is classified Uncertain significance in B4GALT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-17). AlphaMissense: likely benign (0.3188); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with B4GALT1 p.Met366Val (c.1096A>G)?

B4GALT1 p.Met366Val (c.1096A>G) is associated with Inborn genetic diseases (ClinVar).

How common is B4GALT1 p.Met366Val (c.1096A>G) in the general population?

B4GALT1 p.Met366Val (c.1096A>G) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about B4GALT1 p.Met366Val (c.1096A>G)?

AlphaMissense predicts likely benign (score 0.3188) — an in-silico prediction, not a clinical call.

B4GALT1 p.Met366Val

c.1096A>G · rs377678566 · VCV2476078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3188	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -10.56	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 2,544 bp · p 0.073 · regional, not allelic
Overall
CADD	23.4	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 0.0022% South Asian · 2/91,090 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000991% 16/1,614,084 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,545
Admixed American	0.00167%	59,994
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00102%	98,337

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.Met366Val
Coding: c.1096A>G
MANE Select: NM_001497
dbSNP: rs377678566
Type: single nucleotide variant
Location: chr9:33113555 (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 366: a UniProt-annotated variant site (in cdg2d; likely pathogenic); a turn

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

B4GALT1 p.Met366Leu Uncertain significance ★★ ⚠ same residue
B4GALT1 p.Ala17Val Uncertain significance ★★ ⚠ same condition
B4GALT1 p.Asp171Glu Uncertain significance ★★ ⚠ same condition
B4GALT1 p.Gly395Arg Uncertain significance ★★ ⚠ same condition
B4GALT1 p.His176Tyr Uncertain significance ★★ ⚠ same condition
B4GALT1 p.Ile180Val Uncertain significance ★★ ⚠ same condition
B4GALT1 p.Ile300Val Uncertain significance ★★ ⚠ same condition
B4GALT1 p.Pro131Ser 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-met366val (accessed [today's date]).

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