Is BLNK p.Pro98Leu (c.293C>T) pathogenic?

BLNK p.Pro98Leu (c.293C>T) is classified Uncertain significance in BLNK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-28). AlphaMissense: ambiguous (0.3685); Very rare (popmax 0.00329%, sas); Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Pro98Leu (c.293C>T)?

BLNK p.Pro98Leu (c.293C>T) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Pro98Leu (c.293C>T) in the general population?

BLNK p.Pro98Leu (c.293C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about BLNK p.Pro98Leu (c.293C>T)?

AlphaMissense predicts ambiguous (score 0.3685) — an in-silico prediction, not a clinical call.

BLNK p.Pro98Leu

c.293C>T · rs201683834 · VCV839970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3685 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

agammaglobulinemia 4, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.3685	ambiguous
REVEL	0.283	benign-leaning
SaProt	LLR -7.27	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 47 kb · p 0.00042 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,090 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00229% 37/1,614,110 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0844%	1,184
Remaining individualsnot grpmax-eligible	0.0064%	15,623
South Asiangrpmax	0.00329%	30,363
European (non-Finnish)	0.000424%	236,012

Ashkenazi Jewish 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.Pro98Leu
Coding: c.293C>T
MANE Select: NM_013314
dbSNP: rs201683834
Type: single nucleotide variant
Location: chr10:96227478 (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 98: 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 p.Pro98= Likely benign ★★ same residue
BLNK p.Pro98Ala 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

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-pro98leu (accessed [today's date]).

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