Is BLK p.Glu83fs (c.247dup) pathogenic?

BLK p.Glu83fs (c.247dup) is classified Uncertain significance in BLK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-30). Very rare (popmax 0.00568%, nfe); Associated with maturity-onset diabetes of the young type 11.

What condition is associated with BLK p.Glu83fs (c.247dup)?

BLK p.Glu83fs (c.247dup) is associated with maturity-onset diabetes of the young type 11 (ClinVar).

How common is BLK p.Glu83fs (c.247dup) in the general population?

BLK p.Glu83fs (c.247dup) is very rare (popmax 0.00568%, nfe) (gnomAD).

How is MODY inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

BLK p.Glu83fs

c.247dup · VCV3893001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00568%, nfe)

Conditions

maturity-onset diabetes of the young type 11

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 4 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 0.75, phastCons 1
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00568% European (non-Finnish) · 67/1,180,006 alleles

Filtering AF 0.00453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.0044% 71/1,613,658 alleles · very rare exomes 70/1,461,516 · genomes 1/152,142 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00568%	17,612
Remaining individualsnot grpmax-eligible	0.0032%	31,231
African / African-American	0.00267%	37,456

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: BLK
Protein: p.Glu83fs
Coding: c.247dup
MANE Select: NM_001715
Type: Duplication
Location: chr8:11548098 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89
Residue 83: the sh3 domain

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

Disease context

maturity-onset diabetes of the young type 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MODY (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

BLK p.Arg180His Uncertain significance ★★ ⚠ same condition
BLK p.Arg295Trp Uncertain significance ★★ same condition
BLK p.Arg298Gln Uncertain significance ★★ ⚠ same condition
BLK p.Gln226Pro Uncertain significance ★★ ⚠ same condition
BLK p.Gly451Ser Uncertain significance ★★ ⚠ same condition
BLK p.His55Arg Uncertain significance ★★ ⚠ same condition
BLK p.Ile338Thr Uncertain significance ★★ ⚠ same condition
BLK p.Leu381Ser 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/blk-p-glu83fs (accessed [today's date]).

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