Is BLK p.Val28= (c.84C>A) pathogenic?

BLK p.Val28= (c.84C>A) is classified Uncertain significance in BLK (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-08). Absent from gnomAD v4.1; Associated with maturity-onset diabetes of the young type 11.

What condition is associated with BLK p.Val28= (c.84C>A)?

BLK p.Val28= (c.84C>A) is associated with maturity-onset diabetes of the young type 11 (ClinVar).

How common is BLK p.Val28= (c.84C>A) in the general population?

BLK p.Val28= (c.84C>A) is absent from gnomAD v4.1 (gnomAD).

How is MODY inherited?

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

BLK p.Val28=

c.84C>A · rs1585387563 · VCV1029524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

maturity-onset diabetes of the young type 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.95	donor gain · deltas
Pangolin	Δ0.75	gain · loss 0.59 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.37	GERP -0.32
Overall
CADD	16.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BLK
Protein: p.Val28=
Coding: c.84C>A
MANE Select: NM_001715
dbSNP: rs1585387563
Type: single nucleotide variant
Location: chr8:11543308 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89
Residue 28: the 'disordered' region

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.Val28Ile Uncertain significance ★ ⚠ same residue
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

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-val28 (accessed [today's date]).

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