Is BLK p.Val101Ile (c.301G>A) pathogenic?

BLK p.Val101Ile (c.301G>A) is classified Benign in BLK (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.0738); Ultra-rare (popmax 0.0164%, mid); Associated with systemic lupus erythematosus.

What condition is associated with BLK p.Val101Ile (c.301G>A)?

BLK p.Val101Ile (c.301G>A) is associated with systemic lupus erythematosus (ClinVar).

How common is BLK p.Val101Ile (c.301G>A) in the general population?

BLK p.Val101Ile (c.301G>A) is ultra-rare (popmax 0.0164%, mid) (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.Val101Ile (c.301G>A)?

AlphaMissense predicts likely benign (score 0.0738) — an in-silico prediction, not a clinical call.

BLK p.Val101Ile

c.301G>A · rs371256341 · VCV619208

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0738 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

systemic lupus erythematosus

Computational evidence

Protein change
AlphaMissense	0.0738	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.50	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 -3.4	GERP -3.9
Regional constraint	o/e 1.29	unconstrained · MANE · 21 kb · p 7e-14 · regional, not allelic
Overall
CADD	0.287	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00335% 54/1,611,064 alleles · ultra-rare exomes 51/1,458,852 · genomes 3/152,212 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.00481%	20,805
European (non-Finnish)	0.0039%	25,630
South Asian	0.00334%	29,965
Admixed American	0.00168%	59,662

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.Val101Ile
Coding: c.301G>A
MANE Select: NM_001715
dbSNP: rs371256341
Type: single nucleotide variant
Location: chr8:11549055 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89
Residue 101: the sh3 domain

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)

Similar variants

BLK p.Arg131Gln Uncertain significance ★★ ⚠ same condition
BLK p.His55Arg Uncertain significance ★★ ⚠ same condition
BLK c.1030-38C>T Benign ★★ same condition
BLK c.123+88G>T Benign ★★ same condition
BLK c.1313-28C>T Benign ★★ same condition
BLK c.176-104G>A Benign ★★ same condition
BLK c.472+12G>A Benign/Likely benign ★★ same condition
BLK c.-1-105C>G Benign ★★ 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-val101ile (accessed [today's date]).

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