Is BLNK p.Arg427= (c.1281G>A) pathogenic?

BLNK p.Arg427= (c.1281G>A) is classified Likely benign in BLNK (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-10). Absent from gnomAD v4.1; Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Arg427= (c.1281G>A)?

BLNK p.Arg427= (c.1281G>A) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Arg427= (c.1281G>A) in the general population?

BLNK p.Arg427= (c.1281G>A) is absent from gnomAD v4.1 (gnomAD).

BLNK p.Arg427=

c.1281G>A · rs2083339779 · VCV1135132

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

agammaglobulinemia 4, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.031	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.3	GERP 0.94, phastCons 1
Overall
CADD	12.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BLNK
Protein: p.Arg427=
Coding: c.1281G>A
MANE Select: NM_013314
dbSNP: rs2083339779
Type: single nucleotide variant
Location: chr10:96192063 (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 427: 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 p.Arg427Lys Uncertain significance ★ ⚠ same residue
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

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-arg427 (accessed [today's date]).

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