Is BLK p.Pro191Arg (c.572C>G) pathogenic?

BLK p.Pro191Arg (c.572C>G) is classified Uncertain significance in BLK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-21). AlphaMissense: likely benign (0.3392); Ultra-rare (popmax 0.0172%, nfe).

How common is BLK p.Pro191Arg (c.572C>G) in the general population?

BLK p.Pro191Arg (c.572C>G) is ultra-rare (popmax 0.0172%, nfe) (gnomAD).

What do computational predictors say about BLK p.Pro191Arg (c.572C>G)?

AlphaMissense predicts likely benign (score 0.3392) — an in-silico prediction, not a clinical call.

BLK p.Pro191Arg

c.572C>G · rs779113789 · VCV2076024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3392 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3392	likely benign
REVEL	0.408	indeterminate
SaProt	LLR -12.38	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 21 kb · p 7e-14 · regional, not allelic
Overall
CADD	25.6	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 0.0172% European (non-Finnish) · 203/1,180,022 alleles

Filtering AF 0.0152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0145%

Overall 0.0129% 209/1,613,918 alleles · ultra-rare exomes 205/1,461,778 · genomes 4/152,140 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0172%	5,813
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.004%	24,971

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.Pro191Arg
Coding: c.572C>G
MANE Select: NM_001715
dbSNP: rs779113789
Type: single nucleotide variant
Location: chr8:11554842 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89
Residue 191: the sh2 domain

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

Similar variants

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
BLK p.Gln226Pro 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-pro191arg (accessed [today's date]).

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