Is BLNK p.Pro162Ser (c.484C>T) pathogenic?

BLNK p.Pro162Ser (c.484C>T) is classified Uncertain significance in BLNK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: likely benign (0.1599); Ultra-rare (popmax 0.0156%, eas); Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Pro162Ser (c.484C>T)?

BLNK p.Pro162Ser (c.484C>T) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Pro162Ser (c.484C>T) in the general population?

BLNK p.Pro162Ser (c.484C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about BLNK p.Pro162Ser (c.484C>T)?

AlphaMissense predicts likely benign (score 0.1599) — an in-silico prediction, not a clinical call.

BLNK p.Pro162Ser

c.484C>T · rs1554901779 · VCV1719340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1599 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

agammaglobulinemia 4, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.1599	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 23 kb · p 0.96 · regional, not allelic
Overall
CADD	23.4	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 0.0156% East Asian · 7/44,872 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000479% 7/1,461,672 alleles · ultra-rare

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.Pro162Ser
Coding: c.484C>T
MANE Select: NM_013314
dbSNP: rs1554901779
Type: single nucleotide variant
Location: chr10:96223867 (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 162: 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-pro162ser (accessed [today's date]).

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