Is BLNK p.Ala290Val (c.869C>T) pathogenic?

BLNK p.Ala290Val (c.869C>T) is classified Uncertain significance in BLNK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-11). AlphaMissense: likely benign (0.0714); Ultra-rare (popmax 0.0164%, mid); Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Ala290Val (c.869C>T)?

BLNK p.Ala290Val (c.869C>T) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Ala290Val (c.869C>T) in the general population?

BLNK p.Ala290Val (c.869C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about BLNK p.Ala290Val (c.869C>T)?

AlphaMissense predicts likely benign (score 0.0714) — an in-silico prediction, not a clinical call.

BLNK p.Ala290Val

c.869C>T · rs367742561 · VCV2982626

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0714 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

agammaglobulinemia 4, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.0714	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.9	GERP -2.1, phastCons 0.64
Regional constraint	o/e 1.00	unconstrained · MANE · 23 kb · p 0.96 · regional, not allelic
Overall
CADD	15.17	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.0026% 42/1,613,930 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0096%	10,414
Admixed American	0.00333%	29,998
European (non-Finnish)	0.0028%	35,756

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.Ala290Val
Coding: c.869C>T
MANE Select: NM_013314
dbSNP: rs367742561
Type: single nucleotide variant
Location: chr10:96204565 (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 290: 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.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
BLNK p.Arg372Trp 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-ala290val (accessed [today's date]).

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