GHR p.Pro478=
c.1434A>C · rs754637879 · VCV1946428
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00935%, afr)
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 -5.2 | GERP -3.9 |
| Overall | ||
| CADD | 0.304 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00935%
African / African-American · 7/74,900 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.000434%
7/1,613,810 alleles · very rare
exomes 4/1,461,668 · genomes 3/152,142 · 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.Pro478=
- Coding
- c.1434A>C
- MANE Select
- NM_000163
- dbSNP
- rs754637879
- Type
- single nucleotide variant
- Location
- chr5:42718941 (GRCh38)
- Gene constraint
- LOEUF 0.65 · pLI 0.16 (gnomAD)
- Structure
- AlphaFold pLDDT 59.70 · 11 PDB
Similar variants
- GHR p.Pro478Ala 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
- GHR p.Asn115Thr Pathogenic/Likely 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-pro478 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown