Is TRPM1 p.Pro976fs (c.2925del) pathogenic?

TRPM1 p.Pro976fs (c.2925del) is classified Pathogenic in TRPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). Very rare (popmax 0.00167%, amr).

How common is TRPM1 p.Pro976fs (c.2925del) in the general population?

TRPM1 p.Pro976fs (c.2925del) is very rare (popmax 0.00167%, amr) (gnomAD).

TRPM1 p.Pro976fs

c.2925del · rs1183501213 · VCV1451202

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 22 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,012 alleles

Overall 0.000124% 2/1,614,076 alleles · very rare exomes 2/1,461,888 · genomes 0/152,188 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
European (non-Finnish)	8.47e-05%	1,180,013

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.Pro976fs
Coding: c.2925del
MANE Select: NM_001252024
dbSNP: rs1183501213
Type: Deletion
Location: chr15:31032716 (GRCh38)
Gene constraint: LOEUF 0.839 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 66.74

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

Similar variants

TRPM1 p.Pro976= Uncertain significance ★ same residue
TRPM1 p.Pro976Leu Uncertain significance ★ ⚠ same residue
TRPM1 c.1089+3_1089+6del Pathogenic/Likely pathogenic ★★ same type
TRPM1 c.618+3_618+6del Pathogenic/Likely pathogenic ★★ same type
TRPM1 p.Asp113fs Pathogenic/Likely pathogenic ★★ same type
TRPM1 p.Gly161fs Pathogenic/Likely pathogenic ★★ same type
TRPM1 p.Gly279fs Pathogenic ★★ same type
TRPM1 p.Met718fs Pathogenic/Likely pathogenic ★★ 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/trpm1-p-pro976fs (accessed [today's date]).

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