Is BLNK p.Pro44= (c.132T>A) pathogenic?

BLNK p.Pro44= (c.132T>A) is classified Benign/Likely benign in BLNK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-06). Low-frequency (popmax 1.83%, eas); Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Pro44= (c.132T>A)?

BLNK p.Pro44= (c.132T>A) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Pro44= (c.132T>A) in the general population?

BLNK p.Pro44= (c.132T>A) is low-frequency (popmax 1.83%, eas) (gnomAD).

BLNK p.Pro44=

c.132T>A · rs147203646 · VCV708085

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.83%, eas)

Conditions

agammaglobulinemia 4, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.36, phastCons 1
Overall
CADD	9.712	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.83% East Asian · 820/44,874 alleles

Filtering AF 1.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.68%

Overall 0.0918% 1,482/1,614,112 alleles · low-frequency exomes 1,276/1,461,774 · genomes 206/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.83%	55
Finnishnot grpmax-eligible	0.824%	121
Remaining individualsnot grpmax-eligible	0.0832%	1,202
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,933
Admixed American	0.00666%	15,006
African / African-American	0.00666%	15,015
European (non-Finnish)	0.00534%	18,729
South Asian	0.00439%	22,771

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.Pro44=
Coding: c.132T>A
MANE Select: NM_013314
dbSNP: rs147203646
Type: single nucleotide variant
Location: chr10:96242766 (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 44: 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-pro44 (accessed [today's date]).

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