Is B3GALNT2 p.Phe367Val (c.1099T>G) pathogenic?

B3GALNT2 p.Phe367Val (c.1099T>G) is classified Uncertain significance in B3GALNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-12). AlphaMissense: likely benign (0.2391); Very rare (popmax 0.000936%, nfe); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11.

How common is B3GALNT2 p.Phe367Val (c.1099T>G) in the general population?

B3GALNT2 p.Phe367Val (c.1099T>G) is very rare (popmax 0.000936%, nfe) (gnomAD).

How is Walker-Warburg syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about B3GALNT2 p.Phe367Val (c.1099T>G)?

AlphaMissense predicts likely benign (score 0.2391) — an in-silico prediction, not a clinical call.

B3GALNT2 p.Phe367Val

Q: What condition is associated with B3GALNT2 p.Phe367Val (c.1099T>G)?

B3GALNT2 p.Phe367Val (c.1099T>G) is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 (ClinVar).

c.1099T>G · rs1018836177 · VCV2162012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2391 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000936%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.2391	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -6.92	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 5.3	GERP 0.57, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.0016 · regional, not allelic
Overall
CADD	19.93	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 0.000936% European (non-Finnish) · 11/1,174,962 alleles

Filtering AF 0.000502% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000684% 11/1,608,532 alleles · very rare exomes 9/1,456,350 · genomes 2/152,182 · joint denominator

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.Phe367Val
Coding: c.1099T>G
MANE Select: NM_152490
dbSNP: rs1018836177
Type: single nucleotide variant
Location: chr1:235455611 (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

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Walker-Warburg syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (United Kingdom)

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-phe367val (accessed [today's date]).

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