Is B4GALT6 p.Pro36Ser (c.106C>T) pathogenic?

B4GALT6 p.Pro36Ser (c.106C>T) is classified Uncertain significance in B4GALT6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely pathogenic (0.949); Very rare (popmax 0.00134%, afr).

How common is B4GALT6 p.Pro36Ser (c.106C>T) in the general population?

B4GALT6 p.Pro36Ser (c.106C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about B4GALT6 p.Pro36Ser (c.106C>T)?

AlphaMissense predicts likely pathogenic (score 0.949) — an in-silico prediction, not a clinical call.

B4GALT6 p.Pro36Ser

c.106C>T · VCV4191459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.949 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.949	likely pathogenic
REVEL	0.117	moderately benign-leaning
SaProt	LLR -10.16	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 59 kb · p 3.2e-08 · regional, not allelic
Overall
CADD	25.0	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

Grpmax group 0.00134% African / African-American · 1/74,854 alleles

Overall 0.000137% 2/1,461,482 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,854
European (non-Finnish)	8.48e-05%	1,179,738

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: B4GALT6
Protein: p.Pro36Ser
Coding: c.106C>T
MANE Select: NM_004775
Type: single nucleotide variant
Location: chr18:31684321 (GRCh38)
Gene constraint: LOEUF 0.528 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 89.00

Full B4GALT6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

B4GALT6 p.Ile32Val Benign ★★ same type
B4GALT6 c.776+1G>A Uncertain significance ★ same type
B4GALT6 p.Ala304Gly Uncertain significance ★ ⚠ same type
B4GALT6 p.Ala304Thr Uncertain significance ★ ⚠ same type
B4GALT6 p.Arg13Leu Uncertain significance ★ ⚠ same type
B4GALT6 p.Arg13Ser Uncertain significance ★ ⚠ same type
B4GALT6 p.Arg186Gln Uncertain significance ★ ⚠ same type
B4GALT6 p.Arg186Trp Uncertain significance ★ ⚠ same type

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/b4galt6-p-pro36ser (accessed [today's date]).

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