Is MC1R p.Arg151= (c.453C>G) pathogenic?

MC1R p.Arg151= (c.453C>G) is classified Benign/Likely benign in MC1R (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-30). Rare (popmax 0.115%, nfe); Associated with melanoma, cutaneous malignant, susceptibility to, 5.

What condition is associated with MC1R p.Arg151= (c.453C>G)?

MC1R p.Arg151= (c.453C>G) is associated with melanoma, cutaneous malignant, susceptibility to, 5 (ClinVar).

How common is MC1R p.Arg151= (c.453C>G) in the general population?

MC1R p.Arg151= (c.453C>G) is rare (popmax 0.115%, nfe) (gnomAD).

MC1R p.Arg151=

c.453C>G · rs201827012 · VCV321428

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, nfe)

Conditions

melanoma, cutaneous malignant, susceptibility to, 5

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 -4.8	GERP -5.3
Overall
CADD	0.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% European (non-Finnish) · 1,356/1,179,808 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.0923% 1,482/1,606,350 alleles · rare exomes 1,369/1,453,954 · genomes 113/152,396 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.115%	870
Finnishnot grpmax-eligible	0.112%	897
Remaining individualsnot grpmax-eligible	0.0689%	1,452
Middle Eastern	0.0165%	6,062
African / African-American	0.0133%	7,507
Admixed American	0.0117%	8,574
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800

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: MC1R
Protein: p.Arg151=
Coding: c.453C>G
MANE Select: NM_002386
dbSNP: rs201827012
Type: single nucleotide variant
Location: chr16:89919711 (GRCh38)
Gene constraint: LOEUF 1.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.62 · 5 PDB
Residue 151: a UniProt-annotated variant site (correlated with red hair and light skin of type i; binds to alpha-msh but cannot be stimulated to produce camp; reduced expression at the cell surface); an α-helix

Full MC1R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

melanoma, cutaneous malignant, susceptibility to, 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MC1R p.Arg151Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MC1R p.Arg151His Uncertain significance ★ ⚠ same residue
MC1R c.-110A>C Uncertain significance ★★ same condition
MC1R c.-504G>A Uncertain significance ★★ same condition
MC1R c.*739A>T Uncertain significance ★★ same condition
MC1R p.Ala105Thr Uncertain significance ★★ ⚠ same condition
MC1R p.Ala137Ser Uncertain significance ★★ ⚠ same condition
MC1R p.Ala149Thr 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/mc1r-p-arg151 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown