Is BLNK p.Phe68Ser (c.203T>C) pathogenic?

BLNK p.Phe68Ser (c.203T>C) is classified Uncertain significance in BLNK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-28). AlphaMissense: ambiguous (0.5636); Absent from gnomAD v4.1; Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Phe68Ser (c.203T>C)?

BLNK p.Phe68Ser (c.203T>C) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Phe68Ser (c.203T>C) in the general population?

BLNK p.Phe68Ser (c.203T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLNK p.Phe68Ser (c.203T>C)?

AlphaMissense predicts ambiguous (score 0.5636) — an in-silico prediction, not a clinical call.

BLNK p.Phe68Ser

c.203T>C · rs1842470599 · VCV2789566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5636 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

agammaglobulinemia 4, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.5636	ambiguous
REVEL	0.334	indeterminate
SaProt	LLR -3.00	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 47 kb · p 0.00042 · regional, not allelic
Overall
CADD	24.7	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

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.Phe68Ser
Coding: c.203T>C
MANE Select: NM_013314
dbSNP: rs1842470599
Type: single nucleotide variant
Location: chr10:96230795 (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 68: 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-phe68ser (accessed [today's date]).

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