Is TRPM1 p.Pro1069= (c.3207C>T) pathogenic?

TRPM1 p.Pro1069= (c.3207C>T) is classified Likely benign in TRPM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-12). Ultra-rare (popmax 0.0693%, afr).

How common is TRPM1 p.Pro1069= (c.3207C>T) in the general population?

TRPM1 p.Pro1069= (c.3207C>T) is ultra-rare (popmax 0.0693%, afr) (gnomAD).

TRPM1 p.Pro1069=

c.3207C>T · rs377738000 · VCV1097337

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0693%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -20	GERP -5.5
Overall
CADD	0.078	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0693% African / African-American · 52/75,018 alleles

Filtering AF 0.0543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0489%

Overall 0.00936% 151/1,614,082 alleles · ultra-rare exomes 117/1,461,846 · genomes 34/152,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0693%	1,443
South Asian	0.0121%	8,280
European (non-Finnish)	0.00695%	14,390
Remaining individualsnot grpmax-eligible	0.0064%	15,625
Admixed American	0.00167%	60,016
Finnishnot grpmax-eligible	0.00156%	64,024

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: TRPM1
Protein: p.Pro1069=
Coding: c.3207C>T
MANE Select: NM_001252024
dbSNP: rs377738000
Type: single nucleotide variant
Location: chr15:31028418 (GRCh38)

Full TRPM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/trpm1-p-pro1069 (accessed [today's date]).

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