Is BLNK p.Phe114= (c.342C>T) pathogenic?

BLNK p.Phe114= (c.342C>T) is classified Likely benign in BLNK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-03). Very rare (popmax 0.0022%, sas); Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Phe114= (c.342C>T)?

BLNK p.Phe114= (c.342C>T) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Phe114= (c.342C>T) in the general population?

BLNK p.Phe114= (c.342C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

BLNK p.Phe114=

c.342C>T · rs782331274 · VCV2990080

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 -0.077	GERP -0.49
Overall
CADD	11.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,096 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000496% 8/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,548
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000424%	236,012

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.Phe114=
Coding: c.342C>T
MANE Select: NM_013314
dbSNP: rs782331274
Type: single nucleotide variant
Location: chr10:96227429 (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 114: 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-phe114 (accessed [today's date]).

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