Is B4GALNT4 p.Pro582Ser (c.1744C>T) pathogenic?

B4GALNT4 p.Pro582Ser (c.1744C>T) is classified Uncertain significance in B4GALNT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.066); Ultra-rare (popmax 0.013%, eas).

How common is B4GALNT4 p.Pro582Ser (c.1744C>T) in the general population?

B4GALNT4 p.Pro582Ser (c.1744C>T) is ultra-rare (popmax 0.013%, eas) (gnomAD).

What do computational predictors say about B4GALNT4 p.Pro582Ser (c.1744C>T)?

AlphaMissense predicts likely benign (score 0.066) — an in-silico prediction, not a clinical call.

B4GALNT4 p.Pro582Ser

c.1744C>T · rs1283620054 · VCV3132683

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.066 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.013%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.066	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.91	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 -0.7	GERP -1.3
Regional constraint	o/e 1.05	unconstrained · MANE · 12 kb · p 0.075 · regional, not allelic
Overall
CADD	8.888	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 0.013% East Asian · 4/30,686 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00264%

Overall 0.000376% 5/1,330,452 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.013%	7,671
Remaining individualsnot grpmax-eligible	0.00203%	49,380

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: B4GALNT4
Protein: p.Pro582Ser
Coding: c.1744C>T
MANE Select: NM_178537
dbSNP: rs1283620054
Type: single nucleotide variant
Location: chr11:376867 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.89
Residue 582: the 'disordered' region

Full B4GALNT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

B4GALNT4 p.Asn430Ser Benign ★★ same type
B4GALNT4 p.Pro160= Benign ★★ same type
B4GALNT4 p.Ala133Thr Uncertain significance ★ ⚠ same type
B4GALNT4 p.Ala204Ser Uncertain significance ★ ⚠ same type
B4GALNT4 p.Ala208Gly Uncertain significance ★ ⚠ same type
B4GALNT4 p.Ala219Val Uncertain significance ★ ⚠ same type
B4GALNT4 p.Ala294Val Uncertain significance ★ ⚠ same type
B4GALNT4 p.Ala345Val 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/b4galnt4-p-pro582ser (accessed [today's date]).

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