Is BLNK p.Lys391= (c.1173G>A) pathogenic?

BLNK p.Lys391= (c.1173G>A) is classified Likely benign in BLNK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-24). Very rare (popmax 0.00894%, eas); Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Lys391= (c.1173G>A)?

BLNK p.Lys391= (c.1173G>A) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Lys391= (c.1173G>A) in the general population?

BLNK p.Lys391= (c.1173G>A) is very rare (popmax 0.00894%, eas) (gnomAD).

BLNK p.Lys391=

c.1173G>A · rs782786523 · VCV2920339

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00894%, eas)

Conditions

agammaglobulinemia 4, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.277	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP 1.1, phastCons 1
Overall
CADD	8.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00894% East Asian · 4/44,732 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000342% 5/1,460,848 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00894%	11,183
Remaining individualsnot grpmax-eligible	0.0016%	62,456

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.Lys391=
Coding: c.1173G>A
MANE Select: NM_013314
dbSNP: rs782786523
Type: single nucleotide variant
Location: chr10:96196986 (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 391: 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-lys391 (accessed [today's date]).

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