Is BTK p.Arg13= (c.37C>A) pathogenic?

BTK p.Arg13= (c.37C>A) is classified Likely benign in BTK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). Absent from gnomAD v4.1; Associated with isolated growth hormone deficiency type III.

What condition is associated with BTK p.Arg13= (c.37C>A)?

BTK p.Arg13= (c.37C>A) is associated with isolated growth hormone deficiency type III (ClinVar).

How common is BTK p.Arg13= (c.37C>A) in the general population?

BTK p.Arg13= (c.37C>A) is absent from gnomAD v4.1 (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.Arg13=

c.37C>A · rs128620187 · VCV2852256

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

isolated growth hormone deficiency type III

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 3.8	GERP -0.26, phastCons 1
Overall
CADD	9.315	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BTK
Protein: p.Arg13=
Coding: c.37C>A
MANE Select: NM_000061
dbSNP: rs128620187
Type: single nucleotide variant
Location: chrX:101375248 (GRCh38)
Structure: AlphaFold pLDDT 84.95 · 170 PDB
Residue 13: a β-strand; the ph domain; the 'inositol-(1,3,4,5)-tetrakisphosphate 1-binding' region

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.Arg13Ter Pathogenic ★★ same residue
BTK c.1103-2A>G Pathogenic/Likely pathogenic ★★ same condition
BTK c.1349+1G>A Pathogenic ★★ same condition
BTK c.1632-2A>G Pathogenic ★★ same condition
BTK c.588+1G>T Pathogenic ★★ same condition
BTK c.777-1G>A Pathogenic/Likely pathogenic ★★ same condition
BTK c.777-2A>G Pathogenic/Likely pathogenic ★★ same condition
BTK c.839+1G>C 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-arg13 (accessed [today's date]).

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