GHR p.Ser65=
c.195A>G · rs140501920 · VCV197112
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0349%, 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 0.47 | GERP 1.7, phastCons 0.7 |
| Overall | ||
| CADD | 8.662 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0349%
European (non-Finnish) · 411/1,179,204 alleles
Filtering AF
0.0321%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0309%
Overall
0.0264%
426/1,613,112 alleles · ultra-rare
exomes 410/1,460,948 · genomes 16/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0349% | 2,869 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,940 |
| Admixed American | 0.00833% | 12,001 |
| Finnishnot grpmax-eligible | 0.00156% | 64,034 |
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.Ser65=
- Coding
- c.195A>G
- MANE Select
- NM_000163
- dbSNP
- rs140501920
- Type
- single nucleotide variant
- Location
- chr5:42688948 (GRCh38)
- Gene constraint
- LOEUF 0.65 · pLI 0.16 (gnomAD)
- Structure
- AlphaFold pLDDT 59.70 · 11 PDB
- Residue 65
- a β-strand
Similar variants
- GHR p.Ser65Pro Likely pathogenic ★ same residue
- GHR p.Ser65fs Pathogenic ★★ 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-ser65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown