MC2R p.Ala277=
c.831C>A · rs754718068 · VCV3047331
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
MC2R-related 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 0.13 | GERP -2.5, phastCons 0.83 |
| Overall | ||
| CADD | 5.649 | 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
- MC2R
- Protein
- p.Ala277=
- Coding
- c.831C>A
- MANE Select
- NM_000529
- dbSNP
- rs754718068
- Type
- single nucleotide variant
- Location
- chr18:13884688 (GRCh38)
- Gene constraint
- LOEUF 1.39 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.11 · 2 PDB
- Residue 277
- an α-helix
Disease context
MC2R-related disorder
Similar variants
- MC2R p.Ser256Phe Pathogenic/Likely pathogenic ★★ same condition
- MC2R p.Ser74Ile Pathogenic ★★ same condition
- MC2R p.Leu198Pro Likely pathogenic ★ same condition
- MC2R p.Thr159Arg Likely pathogenic ★ ⚠ same condition
- MC2R p.Thr179Met Likely pathogenic ★ ⚠ same condition
- MC2R p.Cys64fs Likely pathogenic ★ same condition
- MC2R p.Arg137Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- MC2R p.Arg146His 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/mc2r-p-ala277 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown