MC3R p.Ser236=
c.708A>G · VCV4945416
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
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 -7.3 | GERP -5.8 |
| Overall | ||
| CADD | 0.615 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,078 alleles
Filtering AF
0.0021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.000496%
8/1,613,886 alleles · very rare
exomes 7/1,461,694 · genomes 1/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,216 |
| East Asian | 0.00446% | 22,431 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,500 |
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.Ser236=
- Coding
- c.708A>G
- MANE Select
- NM_019888
- Type
- single nucleotide variant
- Location
- chr20:56249551 (GRCh38)
- Gene constraint
- LOEUF 1.196 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.32 · 6 PDB
- Residue 236
- an α-helix
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-ser236 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown