Is BLK p.Pro307Ala (c.919C>G) pathogenic?

BLK p.Pro307Ala (c.919C>G) is classified Pathogenic in BLK (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9076); Absent from gnomAD v4.1; Associated with systemic lupus erythematosus.

What condition is associated with BLK p.Pro307Ala (c.919C>G)?

BLK p.Pro307Ala (c.919C>G) is associated with systemic lupus erythematosus (ClinVar).

How common is BLK p.Pro307Ala (c.919C>G) in the general population?

BLK p.Pro307Ala (c.919C>G) is absent from gnomAD v4.1 (gnomAD).

How is Systemic lupus erythematosus inherited?

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

What do computational predictors say about BLK p.Pro307Ala (c.919C>G)?

AlphaMissense predicts likely pathogenic (score 0.9076) — an in-silico prediction, not a clinical call.

BLK p.Pro307Ala

c.919C>G · rs1307379746 · VCV619203

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9076 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

systemic lupus erythematosus

⚠ 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	0.9076	likely pathogenic ✓ concordant with ClinVar
REVEL	0.821	moderately pathogenic-leaning
SaProt	LLR -11.81	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 21 kb · p 7e-14 · regional, not allelic
Overall
CADD	27.5	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.Pro307Ala
Coding: c.919C>G
MANE Select: NM_001715
dbSNP: rs1307379746
Type: single nucleotide variant
Location: chr8:11556804 (GRCh38)

Full BLK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

systemic lupus erythematosus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Systemic lupus erythematosus (Orphanet):

Inheritance: Not applicable
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-5 / 10 000 (France)

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-pro307ala (accessed [today's date]).

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