MC3R p.Pro269=
c.807C>T · rs779397821 · VCV2826710
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00666%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -0.15, phastCons 1 |
| Overall | ||
| CADD | 11.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00666%
Admixed American · 4/60,024 alleles
Filtering AF
0.00225%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00031%
5/1,614,046 alleles · very rare
exomes 5/1,461,742 · genomes 0/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00666% | 15,006 |
| European (non-Finnish) | 8.48e-05% | 1,179,892 |
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
- MC3R
- Protein
- p.Pro269=
- Coding
- c.807C>T
- MANE Select
- NM_019888
- dbSNP
- rs779397821
- Type
- single nucleotide variant
- Location
- chr20:56249650 (GRCh38)
- Gene constraint
- LOEUF 1.196 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.32 · 6 PDB
- Residue 269
- a β-strand
Similar variants
- MC3R p.Leu106Val Uncertain significance ★★ ⚠ same type
- MC3R p.Thr13Ala Uncertain significance ★★ ⚠ same type
- MC3R p.Thr157Asn Uncertain significance ★★ ⚠ same type
- MC3R p.Ile189= Likely benign ★★ same type
- MC3R p.Leu58= Likely benign ★★ same type
- MC3R p.Val44Ile Benign ★★ same type
- MC3R p.Ala139Thr Uncertain significance ★ ⚠ same type
- MC3R p.Ala149Val 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/mc3r-p-pro269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown