Is B4GALNT1 p.Pro64Arg (c.191C>G) pathogenic?

B4GALNT1 p.Pro64Arg (c.191C>G) is classified Uncertain significance in B4GALNT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-09). AlphaMissense: likely benign (0.0894); Very rare (popmax 0.00555%, amr); Associated with Inborn genetic diseases.

What condition is associated with B4GALNT1 p.Pro64Arg (c.191C>G)?

B4GALNT1 p.Pro64Arg (c.191C>G) is associated with Inborn genetic diseases (ClinVar).

How common is B4GALNT1 p.Pro64Arg (c.191C>G) in the general population?

B4GALNT1 p.Pro64Arg (c.191C>G) is very rare (popmax 0.00555%, amr) (gnomAD).

What do computational predictors say about B4GALNT1 p.Pro64Arg (c.191C>G)?

AlphaMissense predicts likely benign (score 0.0894) — an in-silico prediction, not a clinical call.

B4GALNT1 p.Pro64Arg

c.191C>G · rs764035610 · VCV962697

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0894 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00555%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0894	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.77 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.4	GERP -0.49, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,385 bp · p 0.015 · regional, not allelic
Overall
CADD	23.9	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 0.00555% Admixed American · 2/36,034 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.0018% 26/1,445,578 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00555%	18,017
European (non-Finnish)	0.00209%	47,789
Remaining individualsnot grpmax-eligible	0.00181%	55,280

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.Pro64Arg
Coding: c.191C>G
MANE Select: NM_001478
dbSNP: rs764035610
Type: single nucleotide variant
Location: chr12:57631942 (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

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

Similar variants

B4GALNT1 p.Pro64Leu Uncertain significance ★ ⚠ same residue
B4GALNT1 p.Pro64Thr Uncertain significance ★ ⚠ same residue
B4GALNT1 p.Pro64= Likely benign ★ same residue
B4GALNT1 p.Ala277Thr Uncertain significance ★★ ⚠ same condition
B4GALNT1 p.Ala363Gly Uncertain significance ★★ ⚠ same condition
B4GALNT1 p.Arg288His Uncertain significance ★★ ⚠ same condition
B4GALNT1 p.Arg293Trp Uncertain significance ★★ ⚠ same condition
B4GALNT1 p.Arg319His 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-pro64arg (accessed [today's date]).

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