MC4R p.Ser99=
c.297A>G · rs2511560654 · VCV2648770
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 -12 | GERP -5.6 |
| Overall | ||
| CADD | 0.137 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- MC4R
- Protein
- p.Ser99=
- Coding
- c.297A>G
- MANE Select
- NM_005912
- dbSNP
- rs2511560654
- Type
- single nucleotide variant
- Location
- chr18:60372053 (GRCh38)
- Gene constraint
- LOEUF 1.341 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.21 · 13 PDB
- Residue 99
- an α-helix; a UniProt-annotated variant site (risk factor for obesity)
Similar variants
- MC4R p.Ser99Ter Likely pathogenic ★ same residue
- MC4R p.Arg165Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- MC4R p.Arg165Trp Pathogenic/Likely pathogenic ★★ same type
- MC4R p.Asp90Asn Pathogenic ★★ same type
- MC4R p.Cys271Arg Pathogenic/Likely pathogenic ★★ same type
- MC4R p.Cys271Tyr Pathogenic ★★ same type
- MC4R p.Gln156Ter Pathogenic/Likely pathogenic ★★ same type
- MC4R p.Glu61Lys 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/mc4r-p-ser99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown