Is BLNK p.Pro204His (c.611C>A) pathogenic?

BLNK p.Pro204His (c.611C>A) is classified Uncertain significance in BLNK (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-10). AlphaMissense: likely benign (0.2745); Absent from gnomAD v4.1; Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Pro204His (c.611C>A)?

BLNK p.Pro204His (c.611C>A) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Pro204His (c.611C>A) in the general population?

BLNK p.Pro204His (c.611C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLNK p.Pro204His (c.611C>A)?

AlphaMissense predicts likely benign (score 0.2745) — an in-silico prediction, not a clinical call.

BLNK p.Pro204His

c.611C>A · rs2084041054 · VCV856791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2745 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

agammaglobulinemia 4, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.2745	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -7.93	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 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 23 kb · p 0.96 · regional, not allelic
Overall
CADD	22.4	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

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.Pro204His
Coding: c.611C>A
MANE Select: NM_013314
dbSNP: rs2084041054
Type: single nucleotide variant
Location: chr10:96215386 (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 204: 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.Pro204= Likely benign ★ 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-pro204his (accessed [today's date]).

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