Is B3GALNT2 p.Leu289Phe (c.865C>T) pathogenic?

B3GALNT2 p.Leu289Phe (c.865C>T) is classified Uncertain significance in B3GALNT2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-07-29). AlphaMissense: likely benign (0.2092); Ultra-rare (popmax 0.0512%, nfe); Associated with Inborn genetic diseases.

What condition is associated with B3GALNT2 p.Leu289Phe (c.865C>T)?

B3GALNT2 p.Leu289Phe (c.865C>T) is associated with Inborn genetic diseases, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 (ClinVar).

How common is B3GALNT2 p.Leu289Phe (c.865C>T) in the general population?

B3GALNT2 p.Leu289Phe (c.865C>T) is ultra-rare (popmax 0.0512%, nfe) (gnomAD).

What do computational predictors say about B3GALNT2 p.Leu289Phe (c.865C>T)?

AlphaMissense predicts likely benign (score 0.2092) — an in-silico prediction, not a clinical call.

B3GALNT2 p.Leu289Phe

c.865C>T · rs185213208 · VCV660530

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2092 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0512%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2092	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.0016 · regional, not allelic
Overall
CADD	26.7	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 0.0512% European (non-Finnish) · 602/1,175,124 alleles

Filtering AF 0.0478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0465%

Overall 0.0399% 638/1,598,248 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0512%	1,952
Ashkenazi Jewishnot grpmax-eligible	0.031%	3,228
Admixed American	0.0161%	6,213
Remaining individualsnot grpmax-eligible	0.0129%	7,745
African / African-American	0.00944%	10,590
Finnishnot grpmax-eligible	0.0047%	21,282

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: B3GALNT2
Protein: p.Leu289Phe
Coding: c.865C>T
MANE Select: NM_152490
dbSNP: rs185213208
Type: single nucleotide variant
Location: chr1:235458763 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.81

Full B3GALNT2 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

Also linked: muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11

Similar variants

B3GALNT2 c.113-1G>C Likely pathogenic ★★ same condition
B3GALNT2 c.1311+1G>A Likely pathogenic ★★ same condition
B3GALNT2 c.1311+1G>C Likely pathogenic ★★ same condition
B3GALNT2 c.1368+1G>C Pathogenic ★★ same condition
B3GALNT2 c.762+1G>A Likely pathogenic ★★ same condition
B3GALNT2 c.842-1G>A Likely pathogenic ★★ same condition
B3GALNT2 p.Arg143Ter Pathogenic/Likely pathogenic ★★ same condition
B3GALNT2 p.Arg150Ter Pathogenic ★★ 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/b3galnt2-p-leu289phe (accessed [today's date]).

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