Is BLK p.Asp327Val (c.980A>T) pathogenic?

BLK p.Asp327Val (c.980A>T) is classified Conflicting classifications of pathogenicity in BLK (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-09). AlphaMissense: likely benign (0.1381); Ultra-rare (popmax 0.0227%, nfe); Associated with maturity-onset diabetes of the young type 11.

What condition is associated with BLK p.Asp327Val (c.980A>T)?

BLK p.Asp327Val (c.980A>T) is associated with maturity-onset diabetes of the young type 11 (ClinVar).

How common is BLK p.Asp327Val (c.980A>T) in the general population?

BLK p.Asp327Val (c.980A>T) is ultra-rare (popmax 0.0227%, 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.Asp327Val (c.980A>T)?

AlphaMissense predicts likely benign (score 0.1381) — an in-silico prediction, not a clinical call.

BLK p.Asp327Val

c.980A>T · rs138333004 · VCV910816

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1381 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

maturity-onset diabetes of the young type 11

Computational evidence

Protein change
AlphaMissense	0.1381	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -8.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8	GERP -0.25, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 21 kb · p 7e-14 · regional, not allelic
Overall
CADD	20.6	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 0.0227% European (non-Finnish) · 268/1,179,960 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0195%

Overall 0.0199% 321/1,613,978 alleles · ultra-rare exomes 285/1,461,770 · genomes 36/152,208 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0547%	1,829
European (non-Finnish)grpmax	0.0227%	4,403
Remaining individualsnot grpmax-eligible	0.0192%	5,206
Admixed American	0.01%	10,002

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp327Val
Coding: c.980A>T
MANE Select: NM_001715
dbSNP: rs138333004
Type: single nucleotide variant
Location: chr8:11557989 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89
Residue 327: the protein kinase domain

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

For MODY (Orphanet):

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

Similar variants

BLK p.Asp327Asn Uncertain significance ★ ⚠ same residue
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-asp327val (accessed [today's date]).

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