GHR p.Pro149=
c.447A>G · rs149470749 · VCV2896747
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000682%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.68 | GERP -0.82 |
| Overall | ||
| CADD | 6.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000682%
European (non-Finnish) · 8/1,173,052 alleles
Filtering AF
0.000293%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000212%
Overall
0.000498%
8/1,606,318 alleles · very rare
exomes 7/1,454,080 · genomes 1/152,238 · joint denominator
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
- GHR
- Protein
- p.Pro149=
- Coding
- c.447A>G
- MANE Select
- NM_000163
- dbSNP
- rs149470749
- Type
- single nucleotide variant
- Location
- chr5:42699831 (GRCh38)
- Gene constraint
- LOEUF 0.65 · pLI 0.16 (gnomAD)
- Structure
- AlphaFold pLDDT 59.70 · 11 PDB
- Residue 149
- a UniProt-annotated variant site (in lars; disrupts gh binding); an α-helix
Similar variants
- GHR p.Pro149Gln Likely pathogenic ★ same residue
- GHR p.Pro149Ala Uncertain significance ★ ⚠ same residue
- GHR c.266+83G>T Pathogenic/Likely pathogenic ★★ same type
- GHR c.267-2A>G Pathogenic/Likely pathogenic ★★ same type
- GHR c.440-1G>A Pathogenic/Likely pathogenic ★★ same type
- GHR c.618+792A>G Pathogenic/Likely pathogenic ★★ same type
- GHR p.Arg235Ter Pathogenic ★★ same type
- GHR p.Arg61Ter Pathogenic ★★ 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/ghr-p-pro149 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown