MC4R p.Arg7=
c.21T>C · rs760074702 · VCV888708
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0713%, eas)
Conditions
1
obesity disorder
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 -5.4 |
| Overall | ||
| CADD | 1.336 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0713%
East Asian · 32/44,886 alleles
Filtering AF
0.0519%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0452%
Overall
0.00217%
35/1,614,046 alleles · ultra-rare
exomes 34/1,461,854 · genomes 1/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0713% | 1,403 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,830 |
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
- MC4R
- Protein
- p.Arg7=
- Coding
- c.21T>C
- MANE Select
- NM_005912
- dbSNP
- rs760074702
- Type
- single nucleotide variant
- Location
- chr18:60372329 (GRCh38)
- Gene constraint
- LOEUF 1.341 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.21 · 13 PDB
Similar variants
- MC4R p.Arg7His Conflicting classifications of pathogenicity ★ ⚠ same residue
- MC4R p.Arg165Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MC4R p.Cys271Tyr Pathogenic ★★ same condition
- MC4R p.Gln156Ter Pathogenic/Likely pathogenic ★★ same condition
- MC4R p.Glu61Lys Pathogenic/Likely pathogenic ★★ same condition
- MC4R p.Ile316Ser Pathogenic/Likely pathogenic ★★ same condition
- MC4R p.Tyr35Ter Pathogenic ★★ same condition
- MC4R c.-121G>A 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/mc4r-p-arg7 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown