Is BLK p.Pro9= (c.27G>A) pathogenic?

BLK p.Pro9= (c.27G>A) is classified Likely benign in BLK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-03). Ultra-rare (popmax 0.012%, afr); Associated with maturity-onset diabetes of the young type 11.

What condition is associated with BLK p.Pro9= (c.27G>A)?

BLK p.Pro9= (c.27G>A) is associated with maturity-onset diabetes of the young type 11 (ClinVar).

How common is BLK p.Pro9= (c.27G>A) in the general population?

BLK p.Pro9= (c.27G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

How is MODY inherited?

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

BLK p.Pro9=

c.27G>A · rs536630306 · VCV1649647

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.59, phastCons 1
Overall
CADD	11.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/75,002 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00186% 30/1,613,942 alleles · ultra-rare exomes 26/1,461,772 · genomes 4/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,334
East Asian	0.00891%	11,218
South Asian	0.00769%	13,009
Admixed American	0.00167%	60,012
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)	0.000678%	147,500

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.Pro9=
Coding: c.27G>A
MANE Select: NM_001715
dbSNP: rs536630306
Type: single nucleotide variant
Location: chr8:11543251 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89
Residue 9: 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.Pro9Leu 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-pro9 (accessed [today's date]).

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