GHSR p.Arg141Pro
c.422G>C · rs199698243 · VCV1209321
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9969 | likely pathogenic · top 1% in GHSR |
|---|---|---|
| REVEL | 0.958 | strongly pathogenic-leaning |
| SaProt | LLR -15.94 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 1.04 | unconstrained · MANE · 3,249 bp · p 0.34 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00483% | 20,702 |
| African / African-American | 0.00267% | 37,470 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
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
- GHSR
- Protein
- p.Arg141Pro
- Coding
- c.422G>C
- MANE Select
- NM_198407
- dbSNP
- rs199698243
- Type
- single nucleotide variant
- Location
- chr3:172447992 (GRCh38)
- Gene constraint
- LOEUF 1.033 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.75 · 10 PDB
- Residue 141
- an α-helix
Similar variants
- GHSR p.Arg141Leu Uncertain significance ★★ ⚠ same residue
- GHSR p.Arg206Pro Uncertain significance ★★ ⚠ same condition
- GHSR p.Arg237Trp Uncertain significance ★★ ⚠ same condition
- GHSR p.Ile58Met Uncertain significance ★★ ⚠ same condition
- GHSR p.Leu274Phe Uncertain significance ★★ ⚠ same condition
- GHSR p.Leu42Val Uncertain significance ★★ ⚠ same condition
- GHSR p.Lys259Asn Uncertain significance ★★ ⚠ same condition
- GHSR p.Phe220Cys Uncertain significance ★★ ⚠ 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/ghsr-p-arg141pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown