Is BLNK p.Pro345Ser (c.1033C>T) pathogenic?

BLNK p.Pro345Ser (c.1033C>T) is classified Uncertain significance in BLNK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-30). AlphaMissense: likely benign (0.1052); Very rare (popmax 0.00229%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BLNK p.Pro345Ser (c.1033C>T)?

BLNK p.Pro345Ser (c.1033C>T) is associated with Inborn genetic diseases, agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Pro345Ser (c.1033C>T) in the general population?

BLNK p.Pro345Ser (c.1033C>T) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about BLNK p.Pro345Ser (c.1033C>T)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

BLNK p.Pro345Ser

c.1033C>T · rs782110816 · VCV966331

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -6.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.25, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 9,018 bp · p 3.7e-06 · regional, not allelic
Overall
CADD	21.9	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 0.00229% European (non-Finnish) · 27/1,180,022 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00198% 29/1,461,838 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,705
Admixed American	0.00167%	60,020
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Pro345Ser
Coding: c.1033C>T
MANE Select: NM_013314
dbSNP: rs782110816
Type: single nucleotide variant
Location: chr10:96200137 (GRCh38)
Gene constraint: LOEUF 0.517 · pLI 0.90 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.46 · 1 PDB

Full BLNK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: agammaglobulinemia 4, autosomal recessive

Similar variants

BLNK p.Pro345Leu 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-pro345ser (accessed [today's date]).

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