Is BTK p.Val67fs (c.198_199del) pathogenic?

BTK p.Val67fs (c.198199del) is classified Likely pathogenic in BTK (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-09). Associated with BTK-related disorder.

What condition is associated with BTK p.Val67fs (c.198_199del)?

BTK p.Val67fs (c.198_199del) is associated with BTK-related disorder (ClinVar).

BTK p.Val67fs

c.198_199del · VCV4952039

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

BTK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 3.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BTK
Protein: p.Val67fs
Coding: c.198_199del
MANE Select: NM_000061
Type: Deletion
Location: chrX:101374577 (GRCh38)
Structure: AlphaFold pLDDT 84.95 · 170 PDB
Residue 67: the ph domain

Full BTK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BTK-related disorder

Similar variants

BTK p.Arg288Trp Pathogenic/Likely pathogenic ★★ same condition
BTK p.Arg520Gln Pathogenic ★★ same condition
BTK p.Arg525Gln Pathogenic/Likely pathogenic ★★ same condition
BTK p.Arg562Trp Pathogenic ★★ same condition
BTK p.Arg641His Pathogenic ★★ same condition
BTK p.Gly594Glu Pathogenic ★★ same condition
BTK p.His362Arg Pathogenic ★★ same condition
BTK p.Pro80= Pathogenic/Likely pathogenic ★★ 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/btk-p-val67fs (accessed [today's date]).

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