Is BLK p.Val287Met (c.859G>A) pathogenic?

BLK p.Val287Met (c.859G>A) is classified Likely benign in BLK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-21). AlphaMissense: likely benign (0.089); Rare (popmax 0.202%, sas); Associated with maturity-onset diabetes of the young type 11.

What condition is associated with BLK p.Val287Met (c.859G>A)?

BLK p.Val287Met (c.859G>A) is associated with maturity-onset diabetes of the young type 11 (ClinVar).

How common is BLK p.Val287Met (c.859G>A) in the general population?

BLK p.Val287Met (c.859G>A) is rare (popmax 0.202%, sas) (gnomAD).

How is MODY inherited?

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

What do computational predictors say about BLK p.Val287Met (c.859G>A)?

AlphaMissense predicts likely benign (score 0.089) — an in-silico prediction, not a clinical call.

BLK p.Val287Met

c.859G>A · rs1042687 · VCV1331414

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.089 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.202%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

maturity-onset diabetes of the young type 11

Computational evidence

Protein change
AlphaMissense	0.089	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -5.46	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 0.054	GERP -3.9, phastCons 0.003
Regional constraint	o/e 1.29	unconstrained · MANE · 21 kb · p 7e-14 · regional, not allelic
Overall
CADD	18.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.202% South Asian · 184/91,086 alleles

Filtering AF 0.178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.169%

Overall 0.0142% 229/1,614,234 alleles · rare exomes 211/1,461,880 · genomes 18/152,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.202%	495
Remaining individualsnot grpmax-eligible	0.016%	6,251
African / African-American	0.016%	6,256
European (non-Finnish)	0.00195%	51,306

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.Val287Met
Coding: c.859G>A
MANE Select: NM_001715
dbSNP: rs1042687
Type: single nucleotide variant
Location: chr8:11556744 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89
Residue 287: the protein kinase 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-val287met (accessed [today's date]).

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