NTRK2 p.Pro48=
c.144T>C · rs1330378026 · VCV1668643
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 2.9 | GERP -0.76, phastCons 1 |
| Overall | ||
| CADD | 14.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,060 alleles
Overall
0.000248%
4/1,612,768 alleles · ultra-rare
exomes 4/1,460,422 · genomes 0/152,346 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,060 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,246 |
| European (non-Finnish) | 8.47e-05% | 1,180,032 |
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
- NTRK2
- Protein
- p.Pro48=
- Coding
- c.144T>C
- MANE Select
- NM_006180
- dbSNP
- rs1330378026
- Type
- single nucleotide variant
- Location
- chr9:84670892 (GRCh38)
- Gene constraint
- LOEUF 0.123 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.53 · 9 PDB
- Residue 48
- the lrrnt domain
Similar variants
- NTRK2 p.Arg551Gln Likely pathogenic ★★ same type
- NTRK2 p.Tyr434Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- NTRK2 p.Ala440Val Uncertain significance ★★ ⚠ same type
- NTRK2 p.Arg124Gly Uncertain significance ★★ ⚠ same type
- NTRK2 p.Arg478Lys Uncertain significance ★★ same type
- NTRK2 p.Arg57Ile Uncertain significance ★★ ⚠ same type
- NTRK2 p.Arg598His Uncertain significance ★★ ⚠ same type
- NTRK2 p.Arg603His Uncertain significance ★★ ⚠ same type
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/ntrk2-p-pro48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown