Is BLK p.Ile150Val (c.448A>G) pathogenic?

BLK p.Ile150Val (c.448A>G) is classified Uncertain significance in BLK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-19). AlphaMissense: likely benign (0.1215); Very rare (popmax 0.000424%, nfe).

How common is BLK p.Ile150Val (c.448A>G) in the general population?

BLK p.Ile150Val (c.448A>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about BLK p.Ile150Val (c.448A>G)?

AlphaMissense predicts likely benign (score 0.1215) — an in-silico prediction, not a clinical call.

BLK p.Ile150Val

c.448A>G · VCV3682122

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1215 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1215	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -8.11	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 2.5	GERP 0.89, phastCons 0.88
Regional constraint	o/e 1.29	unconstrained · MANE · 21 kb · p 7e-14 · regional, not allelic
Overall
CADD	12.72	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,010 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,898 alleles · very rare exomes 4/1,461,678 · genomes 1/152,220 · joint denominator

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.Ile150Val
Coding: c.448A>G
MANE Select: NM_001715
Type: single nucleotide variant
Location: chr8:11550238 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89
Residue 150: the sh2 domain

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

Similar variants

BLK p.Ile150Asn Uncertain significance ★ ⚠ same residue
BLK p.Arg131Gln Uncertain significance ★★ ⚠ same type
BLK p.Arg180His Uncertain significance ★★ ⚠ same type
BLK p.Arg238Trp Uncertain significance ★★ ⚠ same type
BLK p.Arg295Trp Uncertain significance ★★ same type
BLK p.Arg298Gln Uncertain significance ★★ ⚠ same type
BLK p.Arg466His Uncertain significance ★★ ⚠ same type
BLK p.Asp68Val Uncertain significance ★★ same type

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-ile150val (accessed [today's date]).

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