Is BLNK p.Lys301= (c.903A>G) pathogenic?

BLNK p.Lys301= (c.903A>G) is classified Uncertain significance in BLNK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). Very rare (popmax 0.00133%, afr); Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Lys301= (c.903A>G)?

BLNK p.Lys301= (c.903A>G) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Lys301= (c.903A>G) in the general population?

BLNK p.Lys301= (c.903A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

BLNK p.Lys301=

c.903A>G · rs1253972353 · VCV1965155

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

agammaglobulinemia 4, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.93	GERP 0.72, phastCons 1
Overall
CADD	16.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,924 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000867% 14/1,613,834 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,476
African / African-Americangrpmax	0.00133%	74,924
European (non-Finnish)	0.00102%	98,320

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.Lys301=
Coding: c.903A>G
MANE Select: NM_013314
dbSNP: rs1253972353
Type: single nucleotide variant
Location: chr10:96204088 (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 301: the 'disordered' region

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-lys301 (accessed [today's date]).

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