Is MC1R p.Pro271= (c.813C>T) pathogenic?

MC1R p.Pro271= (c.813C>T) is classified Likely benign in MC1R (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). Very rare (popmax 0.00133%, afr).

How common is MC1R p.Pro271= (c.813C>T) in the general population?

MC1R p.Pro271= (c.813C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

MC1R p.Pro271=

c.813C>T · VCV3543972

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 -2.5	GERP -5.4
Overall
CADD	1.358	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,950 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000744% 12/1,613,778 alleles · very rare exomes 10/1,461,540 · genomes 2/152,238 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,950
European (non-Finnish)	0.000932%	107,262

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.Pro271=
Coding: c.813C>T
MANE Select: NM_002386
Type: single nucleotide variant
Location: chr16:89920071 (GRCh38)
Gene constraint: LOEUF 1.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.62 · 5 PDB
Residue 271: an α-helix

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

Similar variants

MC1R p.Pro271Ala Uncertain significance ★★ ⚠ same residue
MC1R p.Pro271Leu Uncertain significance ★ ⚠ same residue
MC1R c.-110A>C Uncertain significance ★★ same type
MC1R c.-504G>A Uncertain significance ★★ same type
MC1R c.*739A>T Uncertain significance ★★ same type
MC1R p.Ala105Thr Uncertain significance ★★ ⚠ same type
MC1R p.Ala137Ser Uncertain significance ★★ ⚠ same type
MC1R p.Ala149Thr 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/mc1r-p-pro271 (accessed [today's date]).

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