GHSR p.Ala204=
c.612G>C · rs201629989 · VCV1543314
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0402%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.31 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.8 | GERP -3.9 |
| Overall | ||
| CADD | 2.136 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0402%
European (non-Finnish) · 474/1,180,038 alleles
Filtering AF
0.0371%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.036%
Overall
0.033%
532/1,613,886 alleles · ultra-rare
exomes 476/1,461,748 · genomes 56/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0402% | 2,490 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,464 |
| Finnishnot grpmax-eligible | 0.0219% | 4,564 |
| Middle Eastern | 0.0164% | 6,084 |
| East Asian | 0.0156% | 6,411 |
| South Asian | 0.0143% | 7,006 |
| Admixed American | 0.00833% | 11,999 |
| African / African-American | 0.00534% | 18,728 |
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.Ala204=
- Coding
- c.612G>C
- MANE Select
- NM_198407
- dbSNP
- rs201629989
- Type
- single nucleotide variant
- Location
- chr3:172447802 (GRCh38)
- Gene constraint
- LOEUF 1.033 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.75 · 10 PDB
- Residue 204
- a UniProt-annotated variant site (in ghdp; affects cell-surface expression; impairs constitutive activity; does not affect the ability to respond to ghrelin); an α-helix
Similar variants
- GHSR p.Ala204Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
- GHSR p.Arg141Leu Uncertain significance ★★ ⚠ same type
- 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
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-ala204 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown