Is TRPM1 p.Pro976= (c.2928A>G) pathogenic?

TRPM1 p.Pro976= (c.2928A>G) is classified Uncertain significance in TRPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). Absent from gnomAD v4.1.

How common is TRPM1 p.Pro976= (c.2928A>G) in the general population?

TRPM1 p.Pro976= (c.2928A>G) is absent from gnomAD v4.1 (gnomAD).

TRPM1 p.Pro976=

c.2928A>G · rs2140912480 · VCV1437921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.39	donor gain · deltas
Constraint at this position
Conservation	phyloP -0.028	GERP -5.5, phastCons 0.31
Overall
CADD	14.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRPM1
Protein: p.Pro976=
Coding: c.2928A>G
MANE Select: NM_001252024
dbSNP: rs2140912480
Type: single nucleotide variant
Location: chr15:31032713 (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.Pro976Leu Uncertain significance ★ ⚠ same residue
TRPM1 p.Pro976fs Pathogenic ★ same residue
TRPM1 c.1089+1G>A Likely pathogenic ★★ same type
TRPM1 c.2316+1G>A Pathogenic/Likely pathogenic ★★ same type
TRPM1 c.2317-1G>C Likely pathogenic ★★ same type
TRPM1 c.2440-2A>G Likely pathogenic ★★ same type
TRPM1 c.2571+1G>A Likely pathogenic ★★ same type
TRPM1 c.3127+1G>A 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-pro976 (accessed [today's date]).

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