Is BTK p.Thr628fs (c.1881_1882del) pathogenic?

BTK p.Thr628fs (c.18811882del) is classified Pathogenic in BTK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-15). No gnomAD frequency available for this variant; Associated with isolated growth hormone deficiency type III.

What condition is associated with BTK p.Thr628fs (c.1881_1882del)?

BTK p.Thr628fs (c.1881_1882del) is associated with isolated growth hormone deficiency type III (ClinVar).

How common is BTK p.Thr628fs (c.1881_1882del) in the general population?

BTK p.Thr628fs (c.1881_1882del) is no gnomAD frequency available for this variant (gnomAD).

How is Non-acquired isolated growth hormone deficiency inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

BTK p.Thr628fs

c.1881_1882del · rs2520527086 · VCV2138634

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

isolated growth hormone deficiency type III

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (18 of 19, 26 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP -0.99, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BTK
Protein: p.Thr628fs
Coding: c.1881_1882del
MANE Select: NM_000061
dbSNP: rs2520527086
Type: Microsatellite
Location: chrX:101353220 (GRCh38)
Structure: AlphaFold pLDDT 84.95 · 170 PDB
Residue 628: an α-helix; the protein kinase domain

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

Disease context

isolated growth hormone deficiency type III — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-acquired isolated growth hormone deficiency (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

BTK p.Thr628Ser Uncertain significance ★ ⚠ same residue
BTK p.Thr628= Likely benign ★ same residue
BTK p.Lys60del Pathogenic ★★ same condition
BTK p.Phe320fs Pathogenic ★ same condition
BTK p.Ser318fs Pathogenic ★ same condition
BTK p.Ser572fs Pathogenic ★ same condition
BTK c.839+4_839+7del Uncertain significance ★ same condition
BTK c.1103-17CT[4] Likely benign ★ 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-thr628fs (accessed [today's date]).

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