GHSR p.His280=
c.840C>T · VCV4690551
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0401%, eas)
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 -2.8 | GERP -3.9 |
| Overall | ||
| CADD | 1.104 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0401%
East Asian · 18/44,898 alleles
Filtering AF
0.0258%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0213%
Overall
0.00223%
36/1,613,672 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0401% | 2,494 |
| African / African-American | 0.00534% | 18,732 |
| Admixed American | 0.00167% | 59,994 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,440 |
| South Asian | 0.0011% | 91,066 |
| European (non-Finnish) | 0.000932% | 107,274 |
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.His280=
- Coding
- c.840C>T
- MANE Select
- NM_198407
- Type
- single nucleotide variant
- Location
- chr3:172445422 (GRCh38)
- Gene constraint
- LOEUF 1.033 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.75 · 10 PDB
- Residue 280
- an α-helix
Similar variants
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- GHSR p.Arg141Pro Uncertain significance ★★ ⚠ same type
- GHSR p.Arg206Pro Uncertain significance ★★ ⚠ same type
- GHSR p.Arg237Trp Uncertain significance ★★ ⚠ same type
- GHSR p.Arg283Ter Uncertain significance ★★ same type
- GHSR p.Glu73Asp Uncertain significance ★★ ⚠ same type
- GHSR p.Glu9Lys Uncertain significance ★★ ⚠ same type
- GHSR p.Ile167Phe 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/ghsr-p-his280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown