Is BLK p.Ala224= (c.672C>T) pathogenic?

BLK p.Ala224= (c.672C>T) is classified Conflicting classifications of pathogenicity in BLK (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-25). Low-frequency (popmax 1.95%, sas); Associated with maturity-onset diabetes of the young type 11.

What condition is associated with BLK p.Ala224= (c.672C>T)?

BLK p.Ala224= (c.672C>T) is associated with maturity-onset diabetes of the young type 11, systemic lupus erythematosus (ClinVar).

How common is BLK p.Ala224= (c.672C>T) in the general population?

BLK p.Ala224= (c.672C>T) is low-frequency (popmax 1.95%, sas) (gnomAD).

How is MODY inherited?

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

BLK p.Ala224=

c.672C>T · rs201252364 · VCV361484

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.95%, sas)

Conditions

maturity-onset diabetes of the young type 11

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.34	GERP -3.9
Overall
CADD	0.651	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.95% South Asian · 1,780/91,076 alleles

Filtering AF 1.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.85%

Overall 0.119% 1,921/1,614,164 alleles · low-frequency exomes 1,811/1,461,880 · genomes 110/152,284 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.95%	51
Remaining individualsnot grpmax-eligible	0.138%	727
Middle Eastern	0.099%	1,010
East Asian	0.00669%	14,958
African / African-American	0.004%	25,014
European (non-Finnish)	0.00364%	27,442

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.Ala224=
Coding: c.672C>T
MANE Select: NM_001715
dbSNP: rs201252364
Type: single nucleotide variant
Location: chr8:11555384 (GRCh38)

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

Also linked: systemic lupus erythematosus

For MODY (Orphanet):

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

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-ala224 (accessed [today's date]).

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