Is BLNK p.Asp366Glu (c.1098T>G) pathogenic?

BLNK p.Asp366Glu (c.1098T>G) is classified Uncertain significance in BLNK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-04). AlphaMissense: likely pathogenic (0.9113); Very rare (popmax 0.00297%, nfe); Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Asp366Glu (c.1098T>G)?

BLNK p.Asp366Glu (c.1098T>G) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Asp366Glu (c.1098T>G) in the general population?

BLNK p.Asp366Glu (c.1098T>G) is very rare (popmax 0.00297%, nfe) (gnomAD).

What do computational predictors say about BLNK p.Asp366Glu (c.1098T>G)?

AlphaMissense predicts likely pathogenic (score 0.9113) — an in-silico prediction, not a clinical call.

BLNK p.Asp366Glu

c.1098T>G · rs782205113 · VCV1059928

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9113 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

agammaglobulinemia 4, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.9113	likely pathogenic
REVEL	0.427	indeterminate
SaProt	LLR -7.59	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.35	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 0.7	GERP 0.75, phastCons 0.91
Regional constraint	o/e 0.61	unconstrained · MANE · 9,018 bp · p 3.7e-06 · regional, not allelic
Overall
CADD	19.97	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 0.00297% European (non-Finnish) · 35/1,178,448 alleles

Filtering AF 0.00216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00267% 39/1,458,126 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00481%	20,785
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,530
European (non-Finnish)grpmax	0.00297%	33,670

Remaining individuals 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: BLNK
Protein: p.Asp366Glu
Coding: c.1098T>G
MANE Select: NM_013314
dbSNP: rs782205113
Type: single nucleotide variant
Location: chr10:96197061 (GRCh38)
Gene constraint: LOEUF 0.517 · pLI 0.90 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.46 · 1 PDB
Residue 366: the sh2 domain

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

Disease context

agammaglobulinemia 4, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BLNK c.902+2T>C Likely pathogenic ★★ same condition
BLNK p.Ala176Val Uncertain significance ★★ ⚠ same condition
BLNK p.Ala218Thr Uncertain significance ★★ ⚠ same condition
BLNK p.Ala290Val Uncertain significance ★★ ⚠ same condition
BLNK p.Ala88Ser Uncertain significance ★★ ⚠ same condition
BLNK p.Ala92Asp Uncertain significance ★★ ⚠ same condition
BLNK p.Ala92Thr Uncertain significance ★★ ⚠ same condition
BLNK p.Arg282Gln 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/blnk-p-asp366glu (accessed [today's date]).

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