Is B3GLCT c.596+50del pathogenic?

B3GLCT c.596+50del is classified Benign in B3GLCT (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-05). Common (popmax 46.7%, nfe) — too common for a highly-penetrant pathogenic allele.

B3GLCT c.596+50del

Q: How common is B3GLCT c.596+50del in the general population?

B3GLCT c.596+50del is common (popmax 46.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs34409451 · VCV1291733

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 46.7%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +50	near-intronic (+50 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.38	GERP -2.2
Non-coding constraint	Z 1.31	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	5.687	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 46.7% European (non-Finnish) · 540,768/1,158,534 alleles

Filtering AF 46.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 46.5%

Overall 42.1% 668,735/1,586,988 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	61.3%	2
European (non-Finnish)grpmax	46.7%	2
Finnishnot grpmax-eligible	40.7%	2
Remaining individualsnot grpmax-eligible	39.8%	3
Middle Eastern	37.4%	3
Ashkenazi Jewishnot grpmax-eligible	35.5%	3
African / African-American	32.3%	3
Admixed American	29.6%	3
South Asian	23.5%	4
East Asian	4.69%	21

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.596+50del
MANE Select: NM_194318
dbSNP: rs34409451
Type: Deletion
Location: chr13:31261132 (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

Similar variants

B3GLCT c.597-23del Benign ★★ same type
B3GLCT c.71-5del Benign/Likely benign ★★ same type
B3GLCT c.71-6_71-5del Benign/Likely benign ★★ same type
B3GLCT p.Ile356fs Pathogenic ★ same type
B3GLCT p.Leu101fs Pathogenic ★ same type
B3GLCT p.Leu362fs Likely pathogenic ★ same type
B3GLCT p.Phe69fs Likely pathogenic ★ same type
B3GLCT p.Pro112fs Pathogenic ★ 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/b3glct-c-596-plus-50del (accessed [today's date]).

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