Is BLNK p.Val85Met (c.253G>A) pathogenic?

BLNK p.Val85Met (c.253G>A) is classified Uncertain significance in BLNK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-30). AlphaMissense: likely benign (0.1787); Very rare (popmax 0.00446%, eas); Associated with agammaglobulinemia 4, autosomal recessive.

What condition is associated with BLNK p.Val85Met (c.253G>A)?

BLNK p.Val85Met (c.253G>A) is associated with agammaglobulinemia 4, autosomal recessive (ClinVar).

How common is BLNK p.Val85Met (c.253G>A) in the general population?

BLNK p.Val85Met (c.253G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about BLNK p.Val85Met (c.253G>A)?

AlphaMissense predicts likely benign (score 0.1787) — an in-silico prediction, not a clinical call.

BLNK p.Val85Met

c.253G>A · rs781998086 · VCV2195937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

agammaglobulinemia 4, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.1787	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -7.58	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 3.9	GERP -0.35, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 47 kb · p 0.00042 · regional, not allelic
Overall
CADD	24.2	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 0.00446% East Asian · 2/44,890 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.00105% 17/1,614,220 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,445
African / African-American	0.004%	25,027
Finnishnot grpmax-eligible	0.00313%	31,992
Admixed American	0.00167%	60,036
South Asian	0.0011%	91,088
European (non-Finnish)	0.000678%	147,506

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.Val85Met
Coding: c.253G>A
MANE Select: NM_013314
dbSNP: rs781998086
Type: single nucleotide variant
Location: chr10:96227518 (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 85: 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.Val85Ala Uncertain significance ★★ ⚠ same residue
BLNK p.Val85= 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

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-val85met (accessed [today's date]).

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