Is BLK p.Cys319Phe (c.956G>T) pathogenic?

BLK p.Cys319Phe (c.956G>T) is classified Uncertain significance in BLK (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-18). AlphaMissense: likely pathogenic (0.8363); Absent from gnomAD v4.1; Associated with maturity-onset diabetes of the young type 11.

What condition is associated with BLK p.Cys319Phe (c.956G>T)?

BLK p.Cys319Phe (c.956G>T) is associated with maturity-onset diabetes of the young type 11 (ClinVar).

How common is BLK p.Cys319Phe (c.956G>T) in the general population?

BLK p.Cys319Phe (c.956G>T) 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.

What do computational predictors say about BLK p.Cys319Phe (c.956G>T)?

AlphaMissense predicts likely pathogenic (score 0.8363) — an in-silico prediction, not a clinical call.

BLK p.Cys319Phe

c.956G>T · rs1563123027 · VCV1333875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8363 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

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
AlphaMissense	0.8363	likely pathogenic
REVEL	0.209	benign-leaning
SaProt	LLR -12.86	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.7	GERP -0.26, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 21 kb · p 7e-14 · regional, not allelic
Overall
CADD	23.9	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

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.Cys319Phe
Coding: c.956G>T
MANE Select: NM_001715
dbSNP: rs1563123027
Type: single nucleotide variant
Location: chr8:11557965 (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

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-cys319phe (accessed [today's date]).

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