Is BLK p.Pro39Leu (c.116C>T) pathogenic?

BLK p.Pro39Leu (c.116C>T) is classified Benign/Likely benign in BLK (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-11-10). AlphaMissense: likely benign (0.1234); Rare (popmax 0.328%, nfe); Associated with maturity-onset diabetes of the young type 11.

What condition is associated with BLK p.Pro39Leu (c.116C>T)?

BLK p.Pro39Leu (c.116C>T) is associated with maturity-onset diabetes of the young type 11, systemic lupus erythematosus (ClinVar).

How common is BLK p.Pro39Leu (c.116C>T) in the general population?

BLK p.Pro39Leu (c.116C>T) is rare (popmax 0.328%, nfe) (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.Pro39Leu (c.116C>T)?

AlphaMissense predicts likely benign (score 0.1234) — an in-silico prediction, not a clinical call.

BLK p.Pro39Leu

c.116C>T · rs142352008 · VCV258175

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1234 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.328%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

maturity-onset diabetes of the young type 11

Computational evidence

Protein change
AlphaMissense	0.1234	likely benign
REVEL	0.287	benign-leaning
SaProt	LLR -8.67	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 4.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 21 kb · p 7e-14 · regional, not allelic
Overall
CADD	20.4	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 0.328% European (non-Finnish) · 3,870/1,180,026 alleles

Filtering AF 0.319% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.316%

Overall 0.273% 4,403/1,613,148 alleles · rare exomes 4,103/1,460,846 · genomes 300/152,302 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.328%	305
Admixed American	0.302%	332
Middle Eastern	0.297%	337
Remaining individualsnot grpmax-eligible	0.23%	434
Finnishnot grpmax-eligible	0.108%	927
South Asian	0.0615%	1,626
Ashkenazi Jewishnot grpmax-eligible	0.0608%	1,645
African / African-American	0.0546%	1,830
East Asian	0.0156%	6,413

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.Pro39Leu
Coding: c.116C>T
MANE Select: NM_001715
dbSNP: rs142352008
Type: single nucleotide variant
Location: chr8:11543340 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89

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

Also linked: systemic lupus erythematosus

For MODY (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

BLK p.Arg131Gln Uncertain significance ★★ ⚠ same condition
BLK p.Arg180His Uncertain significance ★★ ⚠ same condition
BLK p.Arg295Trp Uncertain significance ★★ same condition
BLK p.Arg298Gln Uncertain significance ★★ ⚠ same condition
BLK p.Gln226Pro Uncertain significance ★★ ⚠ same condition
BLK p.Gly451Ser Uncertain significance ★★ ⚠ same condition
BLK p.His55Arg Uncertain significance ★★ ⚠ same condition
BLK p.Ile338Thr Uncertain significance ★★ ⚠ 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-pro39leu (accessed [today's date]).

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