Is B3GLCT p.Pro112fs (c.335del) pathogenic?

B3GLCT p.Pro112fs (c.335del) is classified Pathogenic in B3GLCT (ClinVar, Single submitter, 3 submitters; last evaluated 2022-06-16). Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with B3GLCT p.Pro112fs (c.335del)?

B3GLCT p.Pro112fs (c.335del) is associated with Inborn genetic diseases (ClinVar).

How common is B3GLCT p.Pro112fs (c.335del) in the general population?

B3GLCT p.Pro112fs (c.335del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

B3GLCT p.Pro112fs

c.335del · rs2137805318 · VCV1210066

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.4	GERP -3.5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,490 alleles

Overall 6.84e-05% 1/1,461,256 alleles · very rare

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: B3GLCT
Protein: p.Pro112fs
Coding: c.335del
MANE Select: NM_194318
dbSNP: rs2137805318
Type: Deletion
Location: chr13:31247086 (GRCh38)
Gene constraint: LOEUF 1.109 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 1 PDB

Full B3GLCT 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

B3GLCT p.Pro112Leu Uncertain significance ★ ⚠ same residue
B3GLCT p.Pro112= Likely benign ★ same residue
B3GLCT c.459+1G>A Pathogenic/Likely pathogenic ★★ same condition
B3GLCT p.Arg377His Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asp469Asn Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asp469Tyr Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asp484Gly Uncertain significance ★★ ⚠ same condition
B3GLCT p.Glu43Asp 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/b3glct-p-pro112fs (accessed [today's date]).

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